Nanomedicine at the Pulmonary Frontier: Immune-Centric Approaches for Respiratory Disease Treatment.

Respiratory diseases (RD) are a group of common ailments with a rapidly increasing global prevalence, posing a significant threat to humanity, especially the elderly population, and imposing a substantial burden on society and the economy. RD represents an unmet medical need that requires the development of viable pharmacotherapies. While various promising strategies have been devised to advance potential treatments for RD, their implementation has been hindered by difficulties in drug delivery, particularly in critically ill patients. Nanotechnology offers innovative solutions for delivering medications to the inflamed organ sites, such as the lungs. Although this approach is enticing, delivering nanomedicine to the lungs presents complex challenges that require sophisticated techniques. In this context, we review the potential of novel nanomedicine-based immunomodulatory strategies that could offer therapeutic benefits in managing this pressing health condition.

[18F]ONO-8430506: A novel radioligand for PET imaging of autotaxin (ATX).

We have prepared and tested radioligand [18F]ONO-8430506 ([18F]8) as a novel ATX PET imaging agent derived from highly potent ATX inhibitor ONO-8430506. Radioligand [18F]8 could be prepared in good and reproducible radiochemical yields of 35 ± 5% (n = 6) using late-stage radiofluorination chemistry. ATX binding analysis showed that 9-benzyl tetrahydro-b-carboline 8 has about five times better inhibitory potency than clinical candidate GLPG1690 and somewhat less inhibitory potency than ATX inhibitor PRIMATX. The binding mode for compound 8 inside the catalytic pocket of ATX using computational modelling and docking protocols revealed that compound 8 resembled a comparable binding mode to that of ATX inhibitor GLPG1690. However, PET imaging studies with radioligand [18F]8 showed only relatively low tumour uptake and retention (SUV60min 0.21 ± 0.03) in the tested 8305C human thyroid tumour model reaching a tumour-to-muscle ratio of âˆ¼ 2.2 after 60 min.

Modelling the climate change impact of mitigation (RCP 2.6) and high emission (RCP 8.5) scenarios on maize yield and possible adaptation measures in different agroclimatic zones of Punjab, India.

BACKGROUND: A simulation study was performed for assessing climate change impact on maize under Representative Concentration Pathways (RCPs 2.6 and 8.5) for Punjab, India. The study area comprised five agroclimatic zones (AZs) including seven locations. The bias corrected temperature and rainfall data from four models (CSIRO-Mk-3-6-0, FIO-ESM, IPSL-CM5A-MR and Ensemble) were used as input in CERES-Maize model which was run with constant management practices for two Punjab maize hybrids (PMH 1 and PMH 2). The maize yield for upcoming 70 years (2025-2095) was simulated and its deviations from the baseline (2010-2021) yield were computed under optimized sowing (early-May to early-July) and current sowing (end-May to end-June) period. RESULTS: With current sowing dates, the maize yield declined under both RCP 2.6 and RCP 8.5 scenarios, respectively in all the AZs, that is, by 4-23% and 60-80% in AZ II, by 5-60% and 60-90% in AZ III, by 9-30% and 50-90% in AZ IV and by 13-40% and 30-90% in AZ V. Though yield decline was lesser under RCP 2.6 as compared to RCP 8.5, but still it indicates that adaptive strategy such as shifting of sowing dates may be helpful in stabilizing the maize yield. CONCLUSION: The results for iterative combinations of sowing period revealed that early June sowing in AZ II for both the hybrids, mid- to end-June (Ludhiana and Amritsar) and end-May to mid-June (Patiala) sowings for PMH 1 were able to nullify the negative impact of climate change. Maize cultivation in AZ IV and AZ V would not be a suitable venture for farmers of the region. © 2023 Society of Chemical Industry.

Fluorine-18 Labelled Radioligands for PET Imaging of Cyclooxygenase-2.

Molecular imaging probes enable the early and accurate detection of disease-specific biomarkers and facilitate personalized treatment of many chronic diseases, including cancer. Among current clinically used functional imaging modalities, positron emission tomography (PET) plays a significant role in cancer detection and in monitoring the response to therapeutic interventions. Several preclinical and clinical studies have demonstrated the crucial involvement of cyclooxygenase-2 (COX-2) isozyme in cancer development and progression, making COX-2 a promising cancer biomarker. A variety of COX-2-targeting PET radioligands has been developed based on anti-inflammatory drugs and selective COX-2 inhibitors. However, many of those suffer from non-specific binding and insufficient metabolic stability. This article highlights examples of COX-2-targeting PET radioligands labelled with the short-lived positron emitter 18F, including radiosynthesis and PET imaging studies published in the last decade (2012-2021).

Comparative transcriptomic analysis of races 1, 2, 5 and 6 of Fusarium oxysporum f.sp. pisi in a susceptible pea host identifies differential pathogenicity profiles.

BACKGROUND: The fungal pathogen Fusarium oxysporum f.sp. pisi (Fop) causes Fusarium wilt in peas. There are four races globally: 1, 2, 5 and 6 and all of these races are present in Australia. Molecular infection mechanisms have been studied in a few other F. oxysporum formae speciales; however, there has been no transcriptomic Fop-pea pathosystem study. RESULTS: A transcriptomic study was carried out to understand the molecular pathogenicity differences between the races. Transcriptome analysis at 20 days post-inoculation revealed differences in the differentially expressed genes (DEGs) in the Fop races potentially involved in fungal pathogenicity variations. Most of the DEGs in all the races were engaged in transportation, metabolism, oxidation-reduction, translation, biosynthetic processes, signal transduction, proteolysis, among others. Race 5 expressed the most virulence-associated genes. Most genes encoding for plant cell wall degrading enzymes, CAZymes and effector-like proteins were expressed in race 2. Race 6 expressed the least number of genes at this time point. CONCLUSION: Fop races deploy various factors and complex strategies to mitigate host defences to facilitate colonisation. This investigation provides an overview of the putative pathogenicity genes in different Fop races during the necrotrophic stage of infection. These genes need to be functionally characterised to confirm their pathogenicity/virulence roles and the race-specific genes can be further explored for molecular characterisation.

In Cellulo Generation of Fluorescent Probes for Live-Cell Imaging of Cylooxygenase-2.

Live-cell imaging with fluorescent probes is an essential tool in chemical biology to visualize the dynamics of biological processes in real-time. Intracellular disease biomarker imaging remains a formidable challenge due to the intrinsic limitations of conventional fluorescent probes and the complex nature of cells. This work reports the in cellulo assembly of a fluorescent probe to image cyclooxygenase-2 (COX-2). We developed celecoxib-azide derivative 14, possessing favorable biophysical properties and excellent COX-2 selectivity profile. In cellulo strain-promoted fluorogenic click chemistry of COX-2-engaged compound 14 with non/weakly-fluorescent compounds 11 and 17 formed fluorescent probes 15 and 18 for the detection of COX-2 in living cells. Competitive binding studies, biophysical, and comprehensive computational analyses were used to describe protein-ligand interactions. The reported new chemical toolbox enables precise visualization and tracking of COX-2 in live cells with superior sensitivity in the visible range.

Synthesis and Biological Evaluation of 1,3,5-Trisubstituted 2-Pyrazolines as Novel Cyclooxygenase-2 Inhibitors with Antiproliferative Activity.

A new series of 1,3,5-trisubstituted 2-pyrazolines for the inhibition of cyclooxygenase-2 (COX-2) were synthesized. The designed structures include a COX-2 pharmacophore SO2 CH3 at the para-position of the phenyl ring located at C-5 of a pyrazoline scaffold. The synthesized compounds were tested for in vitro COX-1/COX-2 inhibition and cell toxicity against human colorectal adenocarcinoma cell lines HT-29. The lead compound (4-chlorophenyl){5-[4-(methanesulfonyl)phenyl]-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl}methanone (16) showed significant COX-2 inhibition (IC50 =0.05±0.01 µM), and antiproliferative activity (IC50 =5.46±4.71 µM). Molecular docking studies showed that new pyrazoline-based compounds interact via multiple hydrophobic and hydrogen-bond interactions with key binding site residues of the COX-2 enzyme.

Phylogenetic relationship between Australian Fusarium oxysporum isolates and resolving the species complex using the multispecies coalescent model.

BACKGROUND: The Fusarium oxysporum species complex (FOSC) is a ubiquitous group of fungal species readily isolated from agroecosystem and natural ecosystem soils which includes important plant and human pathogens. Genetic relatedness within the complex has been studied by sequencing either the genes or the barcoding gene regions within those genes. Phylogenetic analyses have demonstrated a great deal of diversity which is reflected in the differing number of clades identified: three, five and eight. Genetic limitation within the species in the complex has been studied through Genealogical Concordance Phylogenetic Species Recognition (GCPSR) analyses with varying number of phylogenetic 'species' identified ranging from two to 21. Such differing views have continued to confuse users of these taxonomies. RESULTS: The phylogenetic relationships between Australian F. oxysporum isolates from both natural and agricultural ecosystems were determined using three datasets: whole genome, nuclear genes, and mitochondrial genome sequences. The phylogenies were concordant except for three isolates. There were three concordant clades from all the phylogenies suggesting similar evolutionary history for mitochondrial genome and nuclear genes for the isolates in these three clades. Applying a multispecies coalescent (MSC) model on the eight single copy nuclear protein coding genes from the nuclear gene dataset concluded that the three concordant clades correspond to three phylogenetic species within the FOSC. There was 100% posterior probability support for the formation of three species within the FOSC. This is the first report of using the MSC model to estimate species within the F. oxysporum species complex. The findings from this study were compared with previously published phylogenetics and species delimitation studies. CONCLUSION: Phylogenetic analyses using three different gene datasets from Australian F. oxysporum isolates have all supported the formation of three major clades which delineated into three species. Species 2 (Clade 3) may be called F. oxysporum as it contains the neotype for F. oxysporum.

Study of ARIMA and least square support vector machine (LS-SVM) models for the prediction of SARS-CoV-2 confirmed cases in the most affected countries.

Discussions about the recently identified deadly coronavirus disease (COVID-19) which originated in Wuhan, China in December 2019 are common around the globe now. This is an infectious and even life-threatening disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It has rapidly spread to other countries from its originating place infecting millions of people globally. To understand future phenomena, strong mathematical models are required with the least prediction errors. In the present study, autoregressive integrated moving average (ARIMA) and least square support vector machine (LS-SVM) models are applied to the data consisting of daily confirmed cases of SARS-CoV-2 in the most affected five countries of the world for modeling and predicting one-month confirmed cases of this disease. To validate these models, the prediction results were tested by comparing it with testing data. The results revealed better accuracy of the LS-SVM model over the ARIMA model and also suggested a rapid rise of SARS-CoV-2 confirmed cases in all the countries under study. This analysis would help governments to take necessary actions in advance associated with the preparation of isolation wards, availability of medicines and medical staff, a decision on lockdown, training of volunteers, and economic plans.

Genomic and metabolic characterisation of alkaloid biosynthesis by asexual Epichloë fungal endophytes of tall fescue pasture grasses.

Symbiotic associations between tall fescue grasses and asexual Epichloë fungal endophytes exhibit biosynthesis of alkaloid compounds causing both beneficial and detrimental effects. Candidate novel endophytes with favourable chemotypic profiles have been identified in germplasm collections by screening for genetic diversity, followed by metabolite profile analysis in endogenous genetic backgrounds. A subset of candidates was subjected to genome survey sequencing to detect the presence or absence and structural status of known genes for biosynthesis of the major alkaloid classes. The capacity to produce specific metabolites was directly predictable from metabolic data. In addition, study of duplicated gene structure in heteroploid genomic constitutions provided further evidence for the origin of such endophytes. Selected strains were inoculated into meristem-derived callus cultures from specific tall fescue genotypes to perform isogenic comparisons of alkaloid profile in different host backgrounds, revealing evidence for host-specific quantitative control of metabolite production, consistent with previous studies. Certain strains were capable of both inoculation and formation of longer-term associations with a nonhost species, perennial ryegrass (Lolium perenne L.). Discovery and primary characterisation of novel endophytes by DNA analysis, followed by confirmatory metabolic studies, offers improvements of speed and efficiency and hence accelerated deployment in pasture grass improvement programs.

Subcellular differential expression of Ep-ICD in oral dysplasia and cancer is associated with disease progression and prognosis.

BACKGROUND: Identification of patients with oral dysplasia at high risk of cancer development and oral squamous cell carcinoma (OSCC) at increased risk of disease recurrence will enable rigorous personalized treatment. Regulated intramembranous proteolysis of Epithelial cell adhesion molecule (EpCAM) resulting in release of its intracellular domain Ep-ICD into cytoplasm and nucleus triggers oncogenic signaling. We analyzed the expression of Ep-ICD in oral dysplasia and cancer and determined its clinical significance in disease progression and prognosis. METHODS: In a retrospective study, immunohistochemical analysis of nuclear and cytoplasmic Ep-ICD and EpEx (extracellular domain of EpCAM), was carried out in 115 OSCC, 97 oral dysplasia and 105 normal oral tissues, correlated with clinicopathological parameters and disease outcome over 60 months for oral dysplasia and OSCC patients. Disease-free survival (DFS) was determined by Kaplan-Meier method and multivariate Cox regression analysis. RESULTS: In comparison with normal oral tissues, significant increase in nuclear Ep-ICD and membrane EpEx was observed in dysplasia, and OSCC (p = 0.013 and < 0.001 respectively). Oral dysplasia patients with increased overall Ep-ICD developed cancer in short time period (mean = 47 months; p = 0.044). OSCC patients with increased nuclear Ep-ICD and membrane EpEx had significantly reduced mean DFS of 33.7 months (p = 0.018). CONCLUSIONS: Our study provided clinical evidence for Ep-ICD as a predictor of cancer development in patients with oral dysplasia and recurrence in OSCC patients, suggesting its potential utility in enhanced management of those patients detected to have increased risk of progression to cancer and recurrence in OSCC patients.

Pyrimidine-based fluorescent COX-2 inhibitors: synthesis and biological evaluation.

The cyclooxygenase-2 (COX-2) enzyme is overexpressed in a variety of cancers and mediates inflammatory processes that aid the growth and progression of malignancies. Three novel and selective fluorescent COX-2 inhibitors have been designed and synthesized on the basis of previously reported pyrimidine-based COX-2 inhibitors and the 7-nitrobenzofurazan fluorophore. In vitro evaluation of COX-1/COX-2 isozyme inhibition identified N-(2-((7-nitro-benzo[c][1,2,5]oxadiazol-4-yl)amino)propyl)-4-[4-(methylsulfonyl)phenyl]-6-(trifluoro-methyl)-pyrimidin-2-amine (6) as a novel potent and selective COX-2 inhibitor (IC50 = 1.8 µM). Lead compound (6) was further evaluated for its ability to selectively visualize COX-2 isozyme in COX-2 expressing human colon cancer cell line HCA-7 using confocal microscopy experiments.

Nuclear heterogeneous nuclear ribonucleoprotein D is associated with poor prognosis and interactome analysis reveals its novel binding partners in oral cancer.

BACKGROUND: Post-transcriptional regulation by heterogeneous ribonucleoproteins (hnRNPs) is an important regulatory paradigm in cancer development. Our proteomic analysis revealed hnRNPD overexpression in oral dysplasia as compared with normal mucosa; its role in oral carcinogenesis remains unknown. Here in we determined the hnRNPD associated protein networks and its clinical significance in oral squamous cell carcinoma (OSCC). METHODS: Immunoprecipitation (IP) followed by tandem mass spectrometry was used to identify the binding partners of hnRNPD in oral cancer cell lines. Ingenuity pathway analysis (IPA) was carried out to unravel the protein interaction networks associated with hnRNPD and key interactions were confirmed by co-IP-western blotting. hnRNPD expression was analyzed in 183 OSCCs, 44 oral dysplasia and 106 normal tissues using immunohistochemistry (IHC) and correlated with clinico-pathological parameters and follow up data over a period of 91 months. Kaplan-Meier survival and Cox-multivariate-regression analyses were used to evaluate the prognostic significance of hnRNPD in OSCC. RESULTS: We identified 345 binding partners of hnRNPD in oral cancer cells. IPA unraveled novel protein-protein interaction networks associated with hnRNPD and suggested its involvement in multiple cellular processes: DNA repair, replication, chromatin remodeling, cellular proliferation, RNA splicing and stability, thereby directing the fate of oral cancer cells. Protein-protein interactions of hnRNPD with 14-3-3ζ, hnRNPK and S100A9 were confirmed using co-IP-western blotting. IHC analysis showed significant overexpression of nuclear hnRNPD in oral dysplasia [p = 0.001, Odds ratio (OR) = 5.1, 95% CI = 2.1-11.1) and OSCCs (p = 0.001, OR = 8.1, 95% CI = 4.5-14.4) in comparison with normal mucosa. OSCC patients showing nuclear hnRNPD overexpression had significantly reduced recurrence free survival [p = 0.026, Hazard ratio = 1.95, 95% CI = 1.0-3.5] by Kaplan-Meier survival and Cox-multivariate-regression analyses and has potential to define a high-risk subgroup among OSCC patients with nodal negative disease. CONCLUSIONS: Our findings suggest novel functions of hnRNPD in cellular proliferation and survival, besides RNA splicing and stability in oral cancer. Association of nuclear hnRNPD with poor prognosis in OSCC patients taken together with its associated protein networks in oral cancer warrant future studies designed to explore its potential as a plausible novel target for molecular therapeutics.

Prognostic significance of cytoplasmic S100A2 overexpression in oral cancer patients.

BACKGROUND: Oral squamous cell carcinoma (OSCC) patients are at high risk of loco-regional recurrence and 5-year survival rates are about 50%. Identification of patients at high risk of recurrence will enable rigorous personalized post-treatment management. Most novel biomarkers have failed translation for clinical use because of their limited successful validation in external patient cohorts. The aim of this study was to determine the prognostic significance of alterations in sub-cellular expression of S100A2, a pro-tumorigenic calcium binding protein, identified as a candidate biomarker in our proteomic analysis in OSCC and validation of its clinical utility in an external cohort. METHODS: In a retrospective study, immunohistochemical analysis of S100A2 was carried out in 235 Indian OSCC (Test set) and 129 normal oral tissues, correlated with clinicopathological parameters and disease outcome over 122 months for OSCC patients following the REMARK criteria. The findings were validated in an external cohort (Validation set 115 Canadian OSCC and 51 normal tissues) and data analyzed using the R package. RESULTS: Significant increase in cytoplasmic and decrease in nuclear S100A2 expression was observed in OSCC in comparison with normal tissues. Cox multivariable regression analysis internally and externally validated cytoplasmic S100A2 association with tumor recurrence. Kaplan Meier analysis of patients stratified to high and low risk groups showed significantly different recurrence free survival (Test set- log rank test, p = 0.005, median survival 16 and 69 months respectively and Validation set - p < 0.00001, median survival 9.4 and 59.9 months respectively); 86% and 81% of patients who had recurrence were correctly stratified into the high risk group. Seventy percent and 81% patients stratified into low risk group did not show cancer recurrence within 1 year in Test and Validation sets. CONCLUSIONS: Our study provided clinical evidence for the potential of cytoplasmic S100A2 overexpression as a predictor of recurrence risk in OSCC patients. A unique translational aspect of our study is validation of S100A2 as prognostic marker in two independent cohorts (Canadian and Indian) suggesting this protein is likely to find widespread utility in clinical practice for identifying oral cancer patients at high risk of disease recurrence.

S100A7 overexpression is a predictive marker for high risk of malignant transformation in oral dysplasia.

Early detection of oral lesions (OLs) at high risk of cancer development is of utmost importance for intervention. There is an urgent unmet clinical need for biomarkers that allow identification of high-risk OLs. Recently, we identified and verified a panel of five candidate protein biomarkers namely S100A7, prothymosin alpha, 14-3-3ζ, 14-3-3σ and heterogeneous nuclear ribonucleoprotein K using proteomics to distinguish OLs with dysplasia and oral cancers from normal oral tissues. The objective of our study was to evaluate the potential of these candidate protein biomarkers for identification of oral dysplastic lesions at high risk of cancer development. Using immunohistochemistry, we analyzed expressions of these five candidate protein biomarkers in 110 patients with biopsy-proven oral dysplasia and known clinical outcome and determined their correlations with p16 expression and HPV 16/18 status. Kaplan-Meier survival analysis showed reduced oral cancer-free survival (OCFS) of 68.6 months (p = 0.007) in patients showing cytoplasmic S100A7 overexpression when compared to patients with weak or no S100A7 immunostaining in cytoplasm (mean OCFS = 122.8 months). Multivariate Cox regression analysis revealed cytoplasmic S100A7 overexpression as the most significant candidate marker associated with cancer development in dysplastic lesions (p = 0.041, hazard ratio = 2.36). In conclusion, our study suggested the potential of S100A7 overexpression in identifying OLs with dysplasia at high risk of cancer development.

Exploring the global landscape of work-life balance research: A bibliometric and thematic analysis.

The research on work-life balance (WLB) published in journals with a Scopus index between 2011 and 2022 is carefully examined in this work. Our research attempts to clarify the evolution and trends in WLB research and the importance of publications that Scopus indexes. After analyzing 2717 research articles, we found that WLB publications have a significant annual growth rate of 14.71 %, which suggests that the trend continues to grow. Significant changes are seen, with 1888 papers produced between 2017 and 2022 highlighting a notable increase in interest in the field. With 1608 papers, social sciences account for the majority of WLB research. With 54 publications, Griffith University (Australia) is the most affiliated institution. With 30 papers, the "Economic and Social Research Council of the United Kingdom" became the primary source of financing. The most prolific author, with nine publications, is Lingard H. At the same time, co-citation analysis reveals 168 co-cited authors. The United States (USA), the United Kingdom (U.K.), and Australia (A.U.) are the top three producing nations. A thematic analysis reveals ten major WLB themes, from work stress to difficulties with human resource management. This study provides crucial insights for policymakers and leaders to address work-life balance issues effectively. Using tools like Gephi or CiteSpace, we could deepen our understanding through advanced analysis methods such as page rank and network visualization.

Evaluating the Effects of Epichloë Fungal Endophytes of Perennial Ryegrass on the Feeding Behaviour and Life History of Rhopalosiphum padi.

The bird cherry-oat aphid, Rhopalosiphum padi (L.), is an economically significant pest of pasture grasses, the latter being capable of hosting several fungal endophyte-perennial ryegrass symbiota rich in alkaloids and toxic to vertebrates and invertebrates. Measuring aphid feeding behaviour can provide insights into the effectiveness and mode of action of different fungal endophytes. This study investigated the effects of different Epichloë-perennial ryegrass symbiota on the feeding behaviour of R. padi using the electrical penetration graph technique while also assessing the aphid life history. In most cases, endophytes had significant feeding deterrence and paired fecundity and mortality effects. But, in some instances, endophytes with the highest aphid mortality did not significantly deter feeding, suggesting a more complicated scenario of interactions between the relative concentration of metabolites, e.g., host plant defence response metabolites and alkaloids, and/or physical changes to leaf morphology. Overall, this study sheds light on the mode of action of Epichloë endophytes against aphids and highlights the importance of Epichloë-perennial ryegrass symbiota in the management of insect pests such as aphids in pasture-based grazing systems.

Oral ethanol prescribing for alcohol withdrawal syndrome: initial findings and future directions following implementation within a United Kingdom National Health Service setting.

INTRODUCTION: Prescribing of ethanol may be an alternative to benzodiazepines for managing alcohol withdrawal syndrome. We present our experience of oral ethanol prescribing within an acute United Kingdom National Health Service setting. METHODS: A retrospective review of patients presenting with alcohol withdrawal who were managed with oral ethanol or benzodiazepines was performed from data collected across two acute care settings. Ethanol prescribing inclusion: high risk of delirium tremens, or a history of harmful alcohol consumption (typically ≥30 units/day; in which 1 unit = 8 grams of alcohol; one standard United States drink = 14 grams of alcohol) or known to have a history of severe alcohol withdrawal, alcohol-related seizures or delirium tremens. Inverse propensity score weighting was used to partially account for variance between the two patient populations. RESULTS: Fifty (82 per cent male; average age 50.9 years) and 93 (84 per cent male; average age 46.5 years) patients in receipt of benzodiazepines or ethanol, respectively, were included. The likelihood of hospital admission was significantly reduced when individuals were managed with ethanol (odds ratio 0.206 (95 per cent confidence interval; 0.066-0.641), Wald chi-square P = 0.006). In those not admitted, the treatment type had no significant impact on length of stay or the number of occasions a pharmacological agent was required. In those admitted, treatment had no significant effect on length of stay. DISCUSSION: We offer preliminary evidence to support a role of oral ethanol in the management of patients with alcohol withdrawal. We have implemented a robust and translatable guideline. Despite limitations in the data set the impact of ethanol in reducing the likelihood of admission remained significant. CONCLUSIONS: In individuals at significant risk of severe alcohol withdrawal, prescribing ethanol as part of a comprehensive care plan, may reduce unplanned admissions. The preliminary findings presented here warrant further assessment through prospective studies.

Crystalline engineering of FAPbI3 via pyrrolidinium ionic liquid for stable perovskite solar cells with 21.72% efficiency.

Improving the crystallinity of formamidinium triiodide (FAPbI3) perovskite layer is one of the most effective approaches to increase the photovoltaic performance and stability of FAPbI3-based solar cells (FSCs). In the current study, FAPbI3 layers were fabricated through a sequential deposition method. The morphology and crystalline properties of the FAPbI3 layers were modified by controlling the lead iodide (PbI2) precursor by adding pyrrolidinium (Pyr) material into the PbI2 layer and modulating the FAPbI3 crystallization. The Pyr contributed to obtain (001)-preferred FAPbI3 orientation with no yellow photo-inactive phase. Subsequently, it reduced the unreacted PbI2 phase in the perovskite layer and suppressed the defect density, resulting in extended carrier lifetimes and improved ambient air and illumination stabilities. The Pyr-mediated FSCs recorded a champion efficiency of 21.72%, which is higher than that of control FSCs with a maximum efficiency of 19.08%. The developed Pyr-mediated method offers a practical and effective approach to fabricate stable and efficient FSCs.

Secretome proteins as candidate biomarkers for aggressive thyroid carcinomas.

Using proteomics in tandem with bioinformatics, the secretomes of nonaggressive and aggressive thyroid carcinoma (TC) cell lines were analyzed to detect potential biomarkers for tumor aggressiveness. A panel of nine proteins, activated leukocyte cell adhesion molecule (ALCAM/CD166), tyrosine-protein kinase receptor (AXL), amyloid beta A4 protein, amyloid-like protein 2, heterogeneous nuclear ribonucleoprotein K, phosphoglycerate kinase 1, pyruvate kinase isozyme M2, phosphatase 2A inhibitor (SET), and protein kinase C inhibitor protein 1 (14-3-3 zeta) was chosen to confirm their expression in TC patients' sera and tissues. Increased presurgical circulating levels of ALCAM were associated with aggressive tumors (p = 0.04) and presence of lymph node metastasis (p = 0.018). Increased serum AXL levels were associated with extrathyroidal extension (p = 0.027). Furthermore, differential expression of amyloid beta A4 protein, AXL, heterogeneous nuclear ribonucleoprotein K, phosphoglycerate kinase 1, pyruvate kinase muscle isozyme M2, and SET was observed in TC tissues compared to benign nodules. Decreased nuclear expression of AXL can detect malignancy with 90% specificity and 100% sensitivity (AUC = 0.995, p < 0.001). In conclusion, some of these proteins show potential for future development as serum and/or tissue-based biomarkers for TC and warrant further investigation in a large cohort of patients.