Cytosolic DNA sensor AIM2 promotes KRAS-driven lung cancer independent of inflammasomes.

Constitutively active KRAS mutations are among the major drivers of lung cancer, yet the identity of molecular co-operators of oncogenic KRAS in the lung remains ill-defined. The innate immune cytosolic DNA sensor and pattern recognition receptor (PRR) Absent-in-melanoma 2 (AIM2) is best known for its assembly of multiprotein inflammasome complexes and promoting an inflammatory response. Here, we define a role for AIM2, independent of inflammasomes, in KRAS-addicted lung adenocarcinoma (LAC). In genetically defined and experimentally induced (nicotine-derived nitrosamine ketone; NNK) LAC mouse models harboring the KrasG12D driver mutation, AIM2 was highly upregulated compared with other cytosolic DNA sensors and inflammasome-associated PRRs. Genetic ablation of AIM2 in KrasG12D and NNK-induced LAC mouse models significantly reduced tumor growth, coincident with reduced cellular proliferation in the lung. Bone marrow chimeras suggest a requirement for AIM2 in KrasG12D-driven LAC in both hematopoietic (immune) and non-hematopoietic (epithelial) cellular compartments, which is supported by upregulated AIM2 expression in immune and epithelial cells of mutant KRAS lung tissues. Notably, protection against LAC in AIM2-deficient mice is associated with unaltered protein levels of mature Caspase-1 and IL-1ß inflammasome effectors. Moreover, genetic ablation of the key inflammasome adapter, ASC, did not suppress KrasG12D-driven LAC. In support of these in vivo findings, AIM2, but not mature Caspase-1, was upregulated in human LAC patient tumor biopsies. Collectively, our findings reveal that endogenous AIM2 plays a tumor-promoting role, independent of inflammasomes, in mutant KRAS-addicted LAC, and suggest innate immune DNA sensing may provide an avenue to explore new therapeutic strategies in lung cancer.

Abbreviated Urine Collection Compared With 24-Hour Urine Collection for Measuring Creatinine Clearance in Adult Critically Ill Patients: A Systematic Review.

OBJECTIVE: To evaluate the accuracy of abbreviated urine collection (≤12 hours) compared with 24-hour urine collection for measuring creatinine clearance (CrCl) in critically ill adult patients. DATA SOURCES: We searched PubMed, Embase, Web of Science, Google Scholar, and ProQuest Dissertations and Thesis Global; screened reference lists of included studies; and contacted the authors when needed. English studies only were considered with no restriction on dates. STUDY SELECTION AND DATA EXTRACTION: After duplicate removal, 2 reviewers screened titles/abstracts, reviewed full-text articles, and extracted data independently. Studies that compared abbreviated versus 24-hour urine collection for measuring CrCl were included. We assessed the risk of bias using the QUADAS-2 tool. We extracted correlation coefficients, mean prediction errors (ME)-as a measure of bias, and root mean squared prediction errors (RMSE)-as a measure of precision. DATA SYNTHESIS: Five studies were included, comprising 528 adult critically ill adults from surgical, medical, and trauma intensive care units (ICUs). Three studies had high risk of bias, and 2 had low risk. The studies evaluated different durations of urine collection, including 30-minute, 2-hour, 4-hour, 6-hour, and 12-hour. Mean 24-hour CrCl ranged from 57 mL/min/1.73 m2 to 103 mL/min. Abbreviated urine collection led to CrCl that correlated well with the 24-hour measured CrCl (correlation coefficient ranged from 0.8 to 0.95). Mean prediction error ranged from 5 mL/min/1.73 m2 to 16 mL/min (from 8% to 25% of the 24-hour CrCl). Root mean squared prediction error calculated from 1 study was 30.5 mL/min/1.73 m2. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Abbreviated urine collection is used to measure CrCl for renal drug dosing in critically ill patients, but its accuracy is not well-established. CONCLUSIONS: Abbreviated urine collection may overestimate CrCl compared with 24-hour urine collection. Larger, well-conducted studies are needed to evaluate the accuracy of CrCl measured using different durations of urine collection in critically ill patients.

Botulinum toxin augmented surgery versus conventional surgery in the management of large-angle concomitant esotropia: A randomized clinical trial.

BACKGROUND: The surgical management of large-angle concomitant esotropia is challenging with high reoperation rates. This study aims to assess the effectiveness and safety of intraoperative botulinum toxin A (BTA) augmentation compared to surgery alone in large angle concomitant esotropia. MATERIALS AND METHODS: This is a prospective randomized interventional study. Patients with large angle concomitant esotropia (≥55 prism diopter [PD]) were randomly allocated to either surgery only (Group I) or BTA augmented surgery (Group II). The surgical effect in PD/mm was calculated and compared between the study groups at all follow up intervals. Treatment was considered successful if the patients had orthotropia ± 10 PD at their final examinations. RESULTS: A total of 23 patients were included in the study, 11 in Group I and 12 in group II. The surgical effect was significantly greater in Group II compared to Group I at all follow up durations. The 1-year surgical effect was 32.5% greater in Group II compared to Group I (5.99 ± 0.69 vs. 4.52 ± 0.91 PD/mm, respectively, P = 0.001). The success rate was greater for Group II compared to Group I (75% vs. 63.64%, respectively), but this difference was not statistically significant (P = 0.901). CONCLUSION: Botulinum toxin augmented surgery is a good alternative to surgery alone in the treatment of large angle concomitant esotropia. BTA injection exerts a significant augmentation effect on medial rectus muscle recessions.

Gum Arabic assisted the biomass synthesis of bimetallic silver copper oxide nanoparticles using gamma-rays for improving bacterial and viral wound healing: Promising antimicrobial activity against foot and mouth disease.

In this work, gamma irradiation was used to create bimetallic silver­copper oxide nanoparticles (Ag-CuO NPs) in an ecologically acceptable way using gum Arabic (GA) polymer as a capping and reducing agent. Bimetallic Ag-CuO NPs were investigated through UV-Vis. spectroscopy, HR-TEM, SEM, DLS, and XRD examinations. The potency of antimicrobial and antibiofilm activities against a few bacterial isolates and Candida sp. had been investigated. Clinical investigations of 30 cows and 20 buffaloes from different sites in Egypt's Sharkia governorate found ulcerative lesions on the mouth and interdigital region. The cytotoxic assay of the generated NPs on BHK-21 was examined. The bimetallic Ag-CuO NPs had an average diameter of 25.58 nm, and the HR-TEM results showed that they were spherical. According to our results, Ag-CuO NPs exhibited the highest antibacterial efficacy against S. aureus (26.5 mm ZOI), K. pneumoniae (26.0 mm ZOI), and C. albicans (28.5 mm ZOI). The growth of biofilms was also successfully inhibited through the application of Ag-CuO NPs by 88.12 % against S. aureus, 87.08 % against C. albicans, and 74.0 % against B. subtilis. The ulcers on the mouth and foot of diseased animals healed in 4-5 days and 1 week, respectively, following topical application of bimetallic Ag-CuO NPs. The results examined the potential protective effects of a dosage of 3.57 µg/mL on cells before viral infection (cell control). According to our research, bimetallic Ag-CuO NPs limit the development of the virus that causes foot-and-mouth disease (FMD). The reduction of a specific FMD virus's cytopathic impact (CPE) on cell development represented the inhibitory effect when compared to identical circumstances without pretreatment with bimetallic Ag-CuO NPs. Their remarkable antibacterial properties at low concentration and continued-phase stability suggest that they may find widespread use in a variety of pharmacological and biological applications, especially in the wound-healing process.

A survey on the knowledge and attitudes of pharmacists towards the application of antimicrobial therapeutic drug monitoring and its challenges in Qatar.

INTRODUCTION: Therapeutic drug monitoring (TDM) is an integral part of pharmaceutical care. Antimicrobials are amongst the most commonly monitored medications. Therefore, identifying the gaps in antimicrobial pharmacokinetics and TDM knowledge and skills among pharmacists is crucial to optimize TDM application. RESEARCH QUESTION: What is the current knowledge, attitudes and perceived barriers of pharmacists in Qatar towards the application of antimicrobial TDM? STUDY DESIGN: Cross-sectional survey. METHODS: The psychometric validation of the survey underwent 3 stages: domain identification and item generation, content validation, and pilot test. The survey was divided into 4 domains (participant characteristics, knowledge, attitudes, and perceived barriers). It was developed in Survey Monkey and distributed to all pharmacists in Hamad Medical Corporation (HMC) hospitals via email. Data was analyzed using IBM Statistical Package for the Social Sciences (SPSS). Categorical and quantitative variables were expressed as frequencies with percentages and medians with interquartile ranges, respectively. Mann-Whitney U-test was used to test the effect of demographic and professional parameters on the knowledge scores. P values less than 0.05 were considered significant. RESULTS: Forty-nine responses were collected. The median age of respondents was 34 years and 51% of them were males. Most respondents were clinical pharmacists (47%). On average, 44% of knowledge questions were correct, whereas 32% were incorrect and 23% were not sure of the answer. The median knowledge score was 5 out of 10 (interquartile range 2.5-6). Participants with post-graduate degrees or prior pharmacokinetic training showed trends towards higher knowledge scores. Online pharmacokinetics calculators were the most frequently used dose adjustment method. The top perceived barriers for the implementation of antimicrobial TDM were lack of knowledge and lack of educational sessions. CONCLUSIONS: Albeit pharmacists in Qatar had modest level of knowledge about antimicrobial TDM, they had positive attitudes towards TDM and its implications in the clinical practice. Future plans should include providing TDM-related education activities.

Extracorporeal Carbon Dioxide Removal to Avoid Invasive Ventilation During Exacerbations of Chronic Obstructive Pulmonary Disease: VENT-AVOID Trial - A Randomized Clinical Trial.

Rationale: It is unclear whether extracorporeal CO2 removal (ECCO2R) can reduce the rate of intubation or the total time on invasive mechanical ventilation (IMV) in adults experiencing an exacerbation of chronic obstructive pulmonary disease (COPD). Objectives: To determine whether ECCO2R increases the number of ventilator-free days within the first 5 days postrandomization (VFD-5) in exacerbation of COPD in patients who are either failing noninvasive ventilation (NIV) or who are failing to wean from IMV. Methods: This randomized clinical trial was conducted in 41 U.S. institutions (2018-2022) (ClinicalTrials.gov ID: NCT03255057). Subjects were randomized to receive either standard care with venovenous ECCO2R (NIV stratum: n = 26; IMV stratum: n = 32) or standard care alone (NIV stratum: n = 22; IMV stratum: n = 33). Measurements and Main Results: The trial was stopped early because of slow enrollment and enrolled 113 subjects of the planned sample size of 180. There was no significant difference in the median VFD-5 between the arms controlled by strata (P = 0.36). In the NIV stratum, the median VFD-5 for both arms was 5 days (median shift = 0.0; 95% confidence interval [CI]: 0.0-0.0). In the IMV stratum, the median VFD-5 in the standard care and ECCO2R arms were 0.25 and 2 days, respectively; median shift = 0.00 (95% confidence interval: 0.00-1.25). In the NIV stratum, all-cause in-hospital mortality was significantly higher in the ECCO2R arm (22% vs. 0%, P = 0.02) with no difference in the IMV stratum (17% vs. 15%, P = 0.73). Conclusions: In subjects with exacerbation of COPD, the use of ECCO2R compared with standard care did not improve VFD-5. Clinical trial registered with www.clinicaltrials.gov (NCT03255057).

Microplastic accumulation in sewer sediments and its potential entering the environment via combined sewer overflows: a study case in Paris.

During wet weather events, combined sewer overflows (CSOs) transfer large amount of particulate matter and associated pollutants into surrounding water bodies, thereby deteriorating the recipients' ecological health. Resuspension of sewer sediments during these events contributes significantly to pollution level of these discharges. However, how much this in-sewer process contributes to CSOs' quality regarding microplastic (MP) pollution is little known. Therefore, an investigation on sewer deposits inside the Parisian combined sewer network was carried out. The study found high MP concentrations stored in this matrix, ranging from 5 × 103 to 178 × 103 particle/kg dry weight. Polymer composition is similar to what found in raw wastewater, containing a high proportion of polyethylene and polypropylene. Thus, the results indicated the persistence of MPs in sewer network during transport during dry weather periods to treatment facilities. Once resuspension of sewer deposits happens, MPs can be released into water flow and get discharged along with CSOs. This highlights another potential pathway of MPs into freshwater environment.

Promising sensors for pharmaceutical pollutant adsorption using Clar's goblet-based 2D membranes.

This study focuses on the design of new 2D membranes from connected Clar's Goblet as a potential sensor for pharmaceutical pollutants, specifically the painkiller drugs aspirin, paracetamol, ibuprofen, and diclofenac. The electronic, optical, and interaction properties are investigated using density functional theory calculations. The Clar's Goblet membranes (CGMs) that were chosen are semiconductors with an energy gap of around 1.5 eV, according to energy gap calculations and density of states. Molecular electrostatic potential (ESP) analysis shows that CGMs have electrophilic and nucleophilic sites, suggesting their suitability for interacting with pharmaceutical pollutants. The adsorption energies confirm the chemical adsorption of pharmaceutical pollutants with diclofenac showing the strongest adsorption. The UV-Vis absorption spectra of CGMs-drug complexes are analyzed, revealing a redshift compared to the absorption spectrum of CGMs alone, confirming the adsorption of these drugs. Further analysis using hole/electron examinations indicates that the type of excitation is local excitation rather than charge transfer excitation. This study quantitatively characterized hole and electron distribution in excited states using various indices. The analysis revealed local excitation transitions and significant charge transfer between the CGMs molecule and pharmaceutical pollutants. Additionally, non-covalent interaction analysis indicates the presence of van der Waals interactions, highlighting the adsorption behavior of the drugs. These results demonstrate the potential of CGMs as a highly sensitive sensor for pharmaceutical pollutants.

The protease ADAM17 at the crossroads of disease: revisiting its significance in inflammation, cancer, and beyond.

The protease A Disintegrin And Metalloproteinase 17 (ADAM17) plays a central role in the pathophysiology of several diseases. ADAM17 is involved in the cleavage and shedding of at least 80 known membrane-tethered proteins, which subsequently modulate several intracellular signaling pathways, and therefore alter cell behavior. Dysregulated expression and/or activation of ADAM17 has been linked to a wide range of autoimmune and inflammatory diseases, cancer, and cardiovascular disease. In this review, we provide an overview of the current state of knowledge from preclinical models and clinical data on the diverse pathophysiological roles of ADAM17, and discuss the mechanisms underlying ADAM17-mediated protein shedding and the potential therapeutic implications of targeting ADAM17 in these diseases.

Exploring the Potential of Chemically Modified Graphyne Nanodots as an Efficient Adsorbent and Sensitive Detector of Environmental Contaminants: A First Principles Study.

In this study, we investigated the reactivity of γ-graphyne (Gp) and its derivatives, Gp-CH3, Gp-COOH, Gp-CN, Gp-NO2, and Gp-SOH, for the removal of toxic heavy metal ions (Hg+ 2, Pb+ 2, and Cd+ 2) from wastewater. From the analysis of the optimized structures, it was observed that all the compounds exhibited planar geometry. The dihedral angles (C9-C2-C1-C6 and C9-C2-C1-C6) were approximately 180.00°, indicating planarity in all molecular arrangements. To understand the electronic properties of the compounds, the HOMO (EH) and LUMO (EL) energies were calculated, and their energy gaps (Eg) were determined. The EH and EL values ranged between - 6.502 and - 8.192 eV and - 1.864 and - 3.773 eV, respectively, for all the compounds. Comparing the EH values, Gp-NO2 exhibited the most stable HOMO, while Gp-CH3 had the least stable structure. In terms of EL values, Gp-NO2 had the most stable LUMO, while Gp-CH3 was the least stable. The Eg values followed the order: Gp-NO2 < Gp-COOH < Gp-CN < Gp-SOH < Gp-CH3 < Gp, with Gp-NO2 (4.41 eV) having the smallest energy gap. The density of states (DOS) analysis showed that the shape and functional group modifications affected the energy levels. Functionalization with electron-withdrawing (CN, NO2, COOH, SOH) or electron-donating (CH3) groups reduced the energy gap. To specifically target the removal of heavy metal ions, the Gp-NO2 ligand was selected for its high binding energy. Complexes of Gp-NO2-Cd, Gp-NO2-Hg, and Gp-NO2-Pb were optimized, and their properties were analyzed. The complexes were found to be planar, with metal-ligand bond distances within the range of 2.092→3.442 Å. The Gp-NO2-Pb complex exhibited the shortest bond length, indicating a stronger interaction due to the smaller size of Pb+ 2. The computed adsorption energy values (Eads) indicated the stability of the complexes, with values ranging from - 0.035 to -4.199 eV. Non-covalent interaction (NCI) analysis was employed to investigate intermolecular interactions in Gp-NO2 complexes. The analysis revealed distinct patterns of attractive and repulsive interactions, providing valuable insights into the binding preferences and steric effects of heavy metals.

Virtual Care? Telepharmacy in Critical Care Settings for Patient-Centered Care and Multidisciplinary Collaboration: A Scoping Review of Activities, Benefits, Economic Impact, Challenges, and Knowledge Gaps.

Background: Very few studies have investigated telepharmacy (TP) in critical care. This scoping review undertook this task. Methods: We searched the following five electronic databases (PubMed, Embase, WoS, Scopus, CINAHL). Data were extracted from the articles and mapped out. Arksey and O'Malley's 6-step framework was used, and data synthesis identified activities, benefits, economic impact, challenges, and knowledge gaps of TP in critical care. Results: Out of 77 reports retrieved, 14 were included in the review as per inclusion criteria. Eight studies (57%) were published since 2020, and 9 (64%) were from the United States. Tele-ICU was in place before TP implementation in six studies (43%). TP used a range of synchronous/asynchronous communications. Studies reported wide assortment of reactive/scheduled TP activities. Patient outcomes were evaluated in one study of sedation-related TP interventions but they were not different despite improved compliance with sedation protocol. Most common clinical interventions/drugs included glycemic, electrolyte, and antimicrobial therapy management and antithrombotic agents among others. Acceptance of TP interventions was 75% or more in four studies and 51-55% in two studies. Benefits of TP included resolved drug-related problems, increased compliance with guidelines, maintained interactions with other health care providers, and patient safety among others. Three studies (21%) reported cost avoidance with TP interventions. Challenges included communication, intervention documentation, tracking implementation of recommendations, and monetary/financial and legislative/regulatory issues. Knowledge gaps comprised lack of frameworks for implementation/evaluation of TP in critical care, methodological aspects, lack of patient-specific outcomes, as well as institution/health-system aspects, and documentation systems, cost, legislative, and sustainability issues. Conclusions: TP in critical care is underpublished, and comprehensive frameworks for its implementation and evaluation remain lacking. Assessments are needed to evaluate the effect of TP in critical care on patient-specific outcomes, its economic and legal dimensions, methods to sustain it, as well as the role of documentation systems, collaboration models, and institutional characteristics.

Collaborative effect of Csnk1a1 haploinsufficiency and mutant p53 in Myc induction can promote leukemic transformation.

ABSTRACT: It is still not fully understood how genetic haploinsufficiency in del(5q) myelodysplastic syndrome (MDS) contributes to malignant transformation of hematopoietic stem cells. We asked how compound haploinsufficiency for Csnk1a1 and Egr1 in the common deleted region on chromosome 5 affects hematopoietic stem cells. Additionally, Trp53 was disrupted as the most frequently comutated gene in del(5q) MDS using CRISPR/Cas9 editing in hematopoietic progenitors of wild-type (WT), Csnk1a1-/+, Egr1-/+, Csnk1a1/Egr1-/+ mice. A transplantable acute leukemia only developed in the Csnk1a1-/+Trp53-edited recipient. Isolated blasts were indefinitely cultured ex vivo and gave rise to leukemia after transplantation, providing a tool to study disease mechanisms or perform drug screenings. In a small-scale drug screening, the collaborative effect of Csnk1a1 haploinsufficiency and Trp53 sensitized blasts to the CSNK1 inhibitor A51 relative to WT or Csnk1a1 haploinsufficient cells. In vivo, A51 treatment significantly reduced blast counts in Csnk1a1 haploinsufficient/Trp53 acute leukemias and restored hematopoiesis in the bone marrow. Transcriptomics on blasts and their normal counterparts showed that the derived leukemia was driven by MAPK and Myc upregulation downstream of Csnk1a1 haploinsufficiency cooperating with a downregulated p53 axis. A collaborative effect of Csnk1a1 haploinsufficiency and p53 loss on MAPK and Myc upregulation was confirmed on the protein level. Downregulation of Myc protein expression correlated with efficient elimination of blasts in A51 treatment. The "Myc signature" closely resembled the transcriptional profile of patients with del(5q) MDS with TP53 mutation.

Extracorporeal blood purification with Oxiris® filter in critically ill patients with COVID-19 requiring continuous renal replacement therapy.

INTRODUCTION: Severe COVID-19 is associated with a dysregulated immune response that usually leads to cytokine release syndrome. This study aimed to compare the use of extracorporeal blood purification therapy (Oxiris®) versus standard continuous renal replacement therapy (CRRT) in critically-ill patients with severe COVID-19. METHODS: This was a national, multicenter, retrospective study of patients with COVID-19 admitted to the intensive care unit (ICU) between March and October 2020 who required CRRT. Patients were categorized into two groups: Oxiris® CRRT and standard CRRT. The primary outcome was the number of patients alive and ventilator-free at 30-days post-CRRT treatment. Key secondary endpoints included change in inflammatory markers, Sequential Organ Failure Assessment (SOFA) scores, and PaO2/FiO2 ratio at 24- and 72-h post Oxiris® initiation. RESULTS: Thirty-five patients received Oxiris® CRRT and 23 patients received standard CRRT. The primary outcome was 31.4% in the Oxiris® group versus 4.3% in the standard CRRT group (adjusted odds ratio 5.97, 95% confidence interval [CI], 0.64-55.6; p = 0.117). In the Oxiris® group, interleukin-6 (IL-6) concentrations significantly decreased at 24 and 72-h (p = 0.033) and PaO2/FiO2 ratio significantly increased at 24 and 72 h after Oxiris® initiation (p = 0.001). There was no significant change in SOFA scores at 24- and 72-h after Oxiris® initiation. CONCLUSION: The number of patients alive and ventilator-free at 30-days was higher in the Oxiris® group than that in the standard CRRT group; however, the difference did not reach statistical significance after adjusting for the baseline severity of illness. There was a significant reduction in IL-6 and significant improvement in PaO2/FiO2 ratio after Oxiris® CRRT initiation.

Shedding Light on the Role of ERAP1 in Axial Spondyloarthritis.

Spondyloarthritis (SpA) is a multifactorial chronic inflammatory disease affecting the axial skeleton (axSpA) and/or peripheral joints (p-SpA) and entheses. The disease's pathogenesis depends on genetic, immunological, mechanical, and environmental factors. Endoplasmic reticulum aminopeptidase 1 (ERAP1) is a multifunctional enzyme that shapes the peptide repertoire presented by major histocompatibility complex (MHC) class I molecules. Genome-wide association studies (GWAS) have identified different single nucleotide polymorphisms (SNPs) in ERAP1 that are associated with several autoimmune diseases, including axSpA. Therefore, a deeper understanding of the ERAP1 role in axSpA could make it a potential therapeutic target for this disease and offer greater insight into its impact on the immune system. Here, we review the biological functions and structure of ERAP1, discuss ERAP1 polymorphisms and their association with axSpA, highlight the interaction between ERAP1 and human leukocyte antigen (HLA)-B27, and review the association between ERAP1 SNPs and axSpA clinical parameters.

A heterostructural MoS2QDs@UiO-66 nanocomposite for the highly efficient photocatalytic degradation of methylene blue under visible light and simulated sunlight.

The development of recyclable photocatalysts with high activity and stability has piqued the interest of researchers in the field of wastewater treatment. In this study, an ultrasonic probe approach was used to immerse a sequence of heterojunctions formed by metal-organic frameworks (UiO-66) and different amounts of molybdenum disulfide quantum dots (MoS2QDs), resulting in a highly recyclable MoS2QDs@UiO-66 photocatalyst. Multiple advanced techniques, such as XPS, XRD, TEM, XRF, and UV-vis spectrophotometry, were used to characterize and confirm the successful preparation of UIO-66 impregnated with MoS2QDs. The results indicated that the best heterostructure catalyst exhibited superior efficiency in the photocatalytic degradation of methylene blue (MB) in water, achieving approximately 99% removal within 30 minutes under simulated sunlight, while approximately 97% removal under visible light. The outstanding photocatalytic performance is predominantly attributed to the photoinduced separation of carriers in this heterostructure system. This study proposes a unique, simple, and low-cost method for improving the degradation performance of organic contaminants in water.

Experimental and theoretical investigations of the effect of bis-phenylurea-based aliphatic amine derivative as an efficient green corrosion inhibitor for carbon steel in HCl solution.

A novel bis-phenylurea-based aliphatic amine (BPUA) was prepared via a facile synthetic route, and evaluated as a potential green organic corrosion inhibitor for carbon steel in 1.0 M HCl solutions. NMR spectroscopy experiments confirmed the preparation of the targeted structure. The corrosion inhibitory behavior of the prospective green compound was explored experimentally by electrochemical methods and theoretically by DFT-based quantum chemical calculations. Obtained results revealed an outstanding performance of BPUA, with efficiency of 95.1% at the inhibitor concentration of 50 mg L-1 at 25 °C. The novel compound has improved the steel resistivity and noticeably reduced the corrosion rate from 33 to 1.7 mils per year. Furthermore, the adsorption study elucidates that the mechanism of the corrosion inhibition activity obeys Langmuir isotherm with mixed physisorption/chemisorption modes for BPUA derivatives on the steel surface. Calculated Gibb's free energy of the adsorption process ranges from -35 to -37 kJ mol-1. The SEM morphology analysis validates the electrochemical measurements and substantiates the corrosion-inhibiting properties of BPUA. Additionally, the eco-toxicity assessment on human epithelial MCF-10A cells proved the environmental friendliness of the BPUA derivatives. Density functional theory (DFT) calculations correlated the inhibitor's chemical structure with the corresponding inhibitory behavior. Quantum descriptors disclosed the potentiality of BPUA adsorption onto the surface through the heteroatom-based functional groups and aromatic rings.

Ethnicity and gender trends of UK authors in The British Medical Journal and the Lancet over the past two decades: a comprehensive longitudinal analysis.

Background: While gender equity among academic authors has been extensively investigated, there is a significant gap in our understanding of racial/ethnic authorship trends, despite the recognition of barriers to authorship along both ethnic and gender lines. Leveraging the meta-data for all articles published in The British Medical Journal (The BMJ) and the Lancet and between 2002 and 2022 (inclusive), we explore demographic trends among UK academic medicine authors in two of the world's leading British medical journals. Methods: We systematically searched PubMed's MEDLINE for all articles published in The BMJ and Lancet between January 1st 2002 and December 31st 2022. Filtering for articles with a UK affiliation, we predicted gender using a publicly-validated name-to-gender dictionary, while data was analysed to explore and investigate ethnicity using the Consumer Data Research Centre's (CDRC) Ethnicity Estimator. Data was analysed to explore and investigate: (a) the proportion of female/male author publications, (b) the proportion of the various UK author ethnicity groups, and (c) the overlap/intersection between gender and ethnic identities among first and last authors. This comprehensive longitudinal analysis was conducted on 82,143 articles (51,209 from The BMJ and 30,934 from the Lancet) which represents >97% of all published articles between 2002 and 2022. As we sought to understand how academic authorship reflects the diversity of the UK population, we limited our analysis to first and last authors who had a UK affiliation and excluded "news" and "comments" pieces (16,736 articles for The BMJ and 4678 articles from the Lancet). The main outcome measures were the trends in first and last authorship demographics of academic medicine, focusing on the proportion of female/male authors, ethnicity and their intersectionality. Findings: Our findings show that, while women have made substantial headway towards equity among first and last authorship in The BMJ (peaking at 42% and 43%), they remain under-represented in the Lancet (35% and 27%). In both The BMJ and Lancet, Black authors have remained severely under-represented as both first and last authors (below 1% for most of the two decades), while Asian authors have increased proportionally to match their fraction in the general population (ranging from 2 to 10%). Interpretation: Analysis over the past two decades has shown that the gender author gap is decreasing quickly in The BMJ and Lancet. However, despite the two journals' growing focus on structural inequalities in medical academia, little progress has been made in rectifying the large gap between White British authors and other ethnic groups, especially Black authors. Without more awareness, diversity initiatives which have resulted in positive gains for White women do not seem to translate well for authors of colour. Funding: None.

Osteoporosis and fracture as risk factors for self-harm and suicide: a systematic review and meta-analysis.

BACKGROUND: Increase in presentations of self-harm to primary care, a risk factor of suicide, has led to a growing interest in identifying at-risk populations. AIM: To examine whether osteoporosis or fractures are risk factors for self-harm, suicidal ideation, and suicide. DESIGN AND SETTING: This was a systematic review of observational studies in adults (>18 years) that had examined the role of osteoporosis and/or fractures in subsequent self-harm, suicidal ideation, and/or suicide. METHOD: Six databases were searched from inception to July 2019. Additional citation tracking of eligible studies was undertaken in November 2022. Screening, data extraction, and quality assessment of full-text articles were performed independently by at least two authors. Where possible, meta-analysis was run on comparable risk estimates. RESULTS: Fifteen studies were included: two examined the outcome of self-harm, three suicidal ideation, and 10 suicide. In approximately half of studies on osteoporosis, the risk of suicidal ideation and suicide remained significant. However, pooling of adjusted odds ratios from three studies indicated no association between osteoporosis and suicide (1.14, 95% confidence interval = 0.88 to 1.49). Nine studies examined the risk of a mixture of fracture types across different outcomes, limiting comparisons. However, all studies examining vertebral fracture (n = 3) reported a significant adjusted negative association for self-harm and suicide. CONCLUSION: Patients with vertebral fractures, a risk potential factor for suicide, may benefit from clinical case finding for mood disorders with personalised primary care management. However, because of the limited number and quality of studies and mixed findings, further examination of these associations is warranted.

Electronic and optical properties of chemically modified 2D GaAs nanoribbons.

We employed density functional theory calculations to investigate the electronic and optical characteristics of finite GaAs nanoribbons (NRs). Our study encompasses chemical alterations including doping, functionalization, and complete passivation, aimed at tailoring NR properties. The structural stability of these NRs was affirmed by detecting real vibrational frequencies in infrared spectra, indicating dynamical stability. Positive binding energies further corroborated the robust formation of NRs. Analysis of doped GaAs nanoribbons revealed a diverse range of energy gaps (approximately 2.672 to 5.132 eV). The introduction of F atoms through passivation extended the gap to 5.132 eV, while Cu atoms introduced via edge doping reduced it to 2.672 eV. A density of states analysis indicated that As atom orbitals primarily contributed to occupied molecular orbitals, while Ga atom orbitals significantly influenced unoccupied states. This suggested As atoms as electron donors and Ga atoms as electron acceptors in potential interactions. We investigated excited-state electron-hole interactions through various indices, including electron-hole overlap and charge-transfer length. These insights enriched our understanding of these interactions. Notably, UV-Vis absorption spectra exhibited intriguing phenomena. Doping with Te, Cu, W, and Mo induced redshifts, while functionalization induced red/blue shifts in GaAs-34NR spectra. Passivation, functionalization, and doping collectively enhanced electrical conductivity, highlighting the potential for improving material properties. Among the compounds studied, GaAs-34NR-edg-Cu demonstrated the highest electrical conductivity, while GaAs-34NR displayed the lowest. In summary, our comprehensive investigation offers valuable insights into customizing GaAs nanoribbon characteristics, with promising implications for nanoelectronics and optoelectronics applications.