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Abstract During summer, ammonia emissions in Southeast Asia influence air pollution and cloud formation. Convective transport by the South Asian monsoon carries these pollutant air masses into the upper troposphere and lower stratosphere (UTLS), where they accumulate under anticyclonic flow conditions. This air mass accumulation is thought to contribute to particle formation and the development of the Asian Tropopause Aerosol Layer (ATAL). Despite the known influence of ammonia and particulate ammonium on air pollution, a comprehensive understanding of the ATAL is lacking. In this modelling study, the influence of ammonia on particle formation is assessed with emphasis on the ATAL. We use the EMAC chemistry-climate model, incorporating new particle formation parameterisations derived from experiments at the CERN CLOUD chamber. Our diurnal cycle analysis confirms that new particle formation mainly occurs during daylight, with a 10-fold enhancement in rate. This increase is prominent in the South Asian monsoon UTLS, where deep convection introduces high ammonia levels from the boundary layer, compared to a baseline scenario without ammonia. Our model simulations reveal that this ammonia-driven particle formation and growth contributes to an increase of up to 80% in cloud condensation nuclei (CCN) concentrations at cloud-forming heights in the South Asian monsoon region. We find that ammonia profoundly influences the aerosol mass and composition in the ATAL through particle growth, as indicated by an order of magnitude increase in nitrate levels linked to ammonia emissions. However, the effect of ammonia-driven new particle formation on aerosol mass in the ATAL is relatively small. Ammonia emissions enhance the regional aerosol optical depth (AOD) for shortwave solar radiation by up to 70%. We conclude that ammonia has a pronounced effect on the ATAL development, composition, the regional AOD, and CCN concentrations.

Objectives: Chronic obstructive pulmonary disease (COPD) is an inflammatory disease with systemic manifestations. Heart failure (HF) is the most critical heart condition associated with COPD. Lung diseases are probably associated with right ventricular (RV) dysfunction, but few studies have investigated this. In this study, we identified whether the prevalence of RV dysfunction among patients with COPD is higher than that among patients without COPD. Materials and Methods: In this retrospective cross-sectional study, we included active/former smokers over the age of 40 years with pulmonary function testing (PFT) at the American University of Beirut Medical Center from January to December 2014 and echocardiography within 1 year of the PFT. We classified a total of 135 patients into two groups: a COPD group and a non-COPD control group. Results: COPD was significantly associated with increased odds of increased pulmonary vascular resistance (adjusted odds ratio: 1.99, 95% confidence interval: 1.15-3.46), after adjusting for age, gender, smoking, HF, and diastolic dysfunction. However, COPD was not associated with tricuspid annular plane systolic excursion (p=0.15). Conclusion: Echocardiographic RV dysfunction is associated with COPD. Future prospective research can help put things into perspective and help differentiate COPD severity and projection.

Background: Influenza represents a significant global health burden for individuals and society. This study assessed the burden of medically attended influenza at a tertiary medical center in Lebanon to describe the demographics, risk factors, and outcomes prior to the COVID-19 pandemic. Methods: This was a retrospective review of patients who tested positive for the influenza virus during three seasons between July 1, 2016 to June 30, 2019, at the American University of Beirut Medical Center. Results: A total of 2049 patients who tested positive for influenza were analyzed. Influenza A accounted for 79.6 % of cases, and influenza B for 19.7 %, with influenza activity starting in October/November and peaking in December/January. Older age above 65 years (AOR=3.584), obesity (AOR=2.183), and chronic conditions such as chronic lung diseases (AOR=1.832), and bacterial co-infection (AOR= 2.834) were found to be independent risk factors for developing complications. Viral co-infection increased the likelihood of death tenfold. Vaccinated patients had a shorter mean hospital stay duration and a lower intensive care unit admission rate. Conclusion: The burden of medically attended influenza at our tertiary medical center in Lebanon prior to the COVID-19 pandemic was high. Vaccination decreased the likelihood of complications leading to intensive care unit admission in patients at risk.

Abstract DNA polymerase eta (Polη) is the only translesion synthesis polymerase capable of error-free bypass of UV-induced cyclobutane pyrimidine dimers. A deficiency in Polη function is associated with the human disease Xeroderma pigmentosum variant (XPV). We hereby report the case of a 60-year-old woman known for XPV and carrying a Polη Thr191Pro variant in homozygosity. We further characterize the variant in vitro and in vivo, providing molecular evidence that the substitution abrogates polymerase activity and results in UV sensitivity through deficient damage bypass. This is the first functional molecular characterization of a missense variant of Polη, whose reported pathogenic variants have thus far been loss of function truncation or frameshift mutations. Our work allows the upgrading of Polη Thr191Pro from ‘variant of uncertain significance’ to ‘likely pathogenic mutant’, bearing direct impact on molecular diagnosis and genetic counseling. Furthermore, we have established a robust experimental approach that will allow a precise molecular analysis of further missense mutations possibly linked to XPV. Finally, it provides insight into critical Polη residues that may be targeted to develop small molecule inhibitors for cancer therapeutics.

This study aimed to assess volatile impurities and ethanol content in ethanol-based hand sanitizers. A total of 31 different brands of hand sanitizers were analyzed using headspace gas chromatography-mass spectrometry to detect impurities and determine alcohol content for compliance. Volatile impurities were identified through Mass Spectrometry database analysis, and regression analysis was employed to ascertain ethanol percentage. Furthermore, a simulated toxicological analysis was conducted to evaluate the potential toxic effects associated with hand sanitizer usage.The detected impurities primarily included ethyl acetate, benzene, acetone, and acetal, along with contaminations such as isobutanol and non-recommended alcohols. In addition, 71 % of samples contained less than the recommended 60 % v/v alcohol concentration, failing to comply with guidelines from the Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO). Additionally, the simulation study underscored acute and chronic toxicities primarily linked to benzene contamination.Given that some of the studied products are imported while others are locally produced, it is imperative for consumers worldwide to be informed that certain hand sanitizers may not only be ineffective but also contain harmful residues.

Abstract Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the most common enzymopathies in humans, present in approximately half a billion people worldwide. More than 230 clinically relevant G6PD mutations of different classes have been reported to date. We hereby describe a patient with chronic hemolysis who presents a substitution of arginine by glycine at position 219 in G6PD protein. The variant was never described in an original publication or characterized on a molecular level. In the present study, we provide structural and biochemical evidence for the molecular basis of its pathogenicity. When compared to the wild-type enzyme, the Arg219Gly mutation markedly reduces the catalytic activity by 50-fold while having a negligible effect on substrate binding affinity. The mutation preserves secondary protein structure, but greatly decreases stability at higher temperatures and to trypsin digestion. Size exclusion chromatography elution profiles show monomeric and dimeric forms for the mutant, but only the latter for the wild-type form, suggesting a critical role of arginine 219 in G6PD dimer formation. Our findings have implications in the development of small molecule activators, with the goal of rescuing the phenotype observed in this and possibly other related mutants.

This study explored how experienced faculty are using social media to support student learning. It analyzed the types of social media learning activities (SMLAs), their design, the cognitive processes that they support, and the types of knowledge that students engage in when completing SMLAs. Data gathered from five different cases of six faculty using social media in their courses revealed that social media has the potential to support student learning and promote different levels of cognitive processes and types of knowledge. Results also revealed that experienced faculty select social media tools based on their technology features or their popularity in the field of study, and they recommend integrating several media sources in the design of a single SMLA. Furthermore, this study suggested that experienced faculty who use social media, specifically wikis and blogs, use them as Learning Management Systems (LMS). Finally, the social factor of social media was not evident in the design of the learning activities, and faculty reported promoting more dialogue in their revised SMLA. The findings of this study yielded significant considerations for faculty when designing SMLA.

The anticancer efficacy of Sudocetaxel Zendusortide (TH1902), a peptide-drug conjugate internalized through a sortilin-mediated process, was assessed in a triple-negative breast cancer-derived MDA-MB-231 immunocompromised xenograft tumor model where complete tumor regression was observed for more than 40 days after the last treatment. Surprisingly, immunohistochemistry analysis revealed high staining of STING, a master regulator in the cancer-immunity cycle. A weekly administration of TH1902 as a single agent in a murine B16-F10 melanoma syngeneic tumor model demonstrated superior tumor growth inhibition than did docetaxel. A net increase in CD45 leukocyte infiltration within TH1902-treated tumors, especially for tumor-infiltrating lymphocytes and tumor-associated macrophages was observed. Increased staining of perforin, granzyme B, and caspase-3 was suggestive of elevated cytotoxic T and natural killer cell activities. Combined TH1902/anti-PD-L1 treatment led to increases in tumor growth inhibition and median animal survival. TH1902 inhibited cell proliferation and triggered apoptosis and senescence in B16-F10 cells in vitro, while inducing several downstream effectors of the cGAS/STING pathway and the expression of MHC-I and PD-L1. This is the first evidence that TH1902 exerts its antitumor activity, in part, through modulation of the immune tumor microenvironment and that the combination of TH1902 with checkpoint inhibitors (anti-PD-L1) could lead to improved clinical outcomes.

BackgroundOvarian Cancer (OC) stands as the most lethal gynecological malignancy, presenting an urgent clinical challenge in the quest to improve response rates. One approach to address this challenge is through drug repurposing, exemplified by the investigation of metabolic-modulating drugs such as Metformin (MTF) and Simvastatin (SIM). This study aims to explore the molecular mechanisms contributing to the potential synergistic anti-cancer effects between MTF and SIM on ovarian cancer cells.MethodsWe assessed the effects of the combination on the proliferation and viability of two cell lines OVCAR-3 and SKOV-3. IC50 concentrations of MTF and SIM were determined using a proliferation assay, followed by subtoxic concentrations to explore the potential synergistic effects on the viability of both cell lines. Transcriptomic analysis was conducted on OVCAR-3 treated cells, and the findings were validated by assessing the expression levels of differentially expressed genes (DEGs) through real-time PCR in both cell lines SK-OV-3 and OVCAR-3.ResultsCytotoxicity analysis guided the selection of treatment concentrations as such MTF 10 mM and SIM 5 μM. The combined treatment of MTF and SIM demonstrated a synergistic inhibition of proliferation and viability in both cell lines. In OVCAR-3, exclusive identification of 507 DEGs was seen in the combination arm. Upregulation of FOXO3, RhoA, and TNFα, along with downregulation of PIK3R1, SKP2, and ATP6V1D levels, was observed in OVCAR-3 treated cells. Real-time PCR validation confirmed the consistency of expression levels for the mentioned DEGs.ConclusionOur data strongly supports the presence of synergy between MTF and SIM in OC cells. The combination's effect is associated with the dysregulation of genes in the key regulators AMPK and mTOR alongside other interconnected pathways.

Background. Colchicine has shown potential cardioprotective effects owing to its broad anti-inflammatory properties. We performed a meta-analysis to assess its safety and efficacy in secondary prevention in patients with established coronary artery disease (CAD). Methods. We searched Ovid Healthstar, MEDLINE, and Embase (inception to May 2022) for randomized controlled trials (RCTs) evaluating the cardiovascular effects of colchicine compared with placebo or usual care in patients with CAD. Study-level data on efficacy and safety outcomes were pooled using the Peto method. The primary outcome was the composite of cardiovascular (CV) death, myocardial infarction (MI), or stroke. Results. A total of 8 RCTs were included with a follow-up duration of ≥1 month, comprising a total of 12,151 patients. Compared with placebo or usual care, colchicine was associated with a significant risk reduction in the primary outcome (odds ratio (OR) 0.70, 95% CI 0.60 to 0.83, P

Background. Rates of major bleeding and intraprocedural thrombotic events (IPTE) in the setting of percutaneous coronary intervention (PCI) using weight-adjusted unfractionated heparin (UFH) without activated clotting time (ACT) monitoring are not known. Methods. We reviewed 2,748 consecutive patients who underwent coronary angiography at our tertiary care university hospital between January 2017 and December 2020. All patients who underwent PCI with weight-adjusted UFH without ACT guidance were considered for further analysis. Major bleeding complications occurring within 48 hours of PCI were collected from patients’ medical records. IPTE were collected independently by two interventional cardiologists after review of coronary angiograms. Results. There were 718 patients included in the analysis (65.4 ± 12.2 years old; 81.3% male). In total, 45 patients (7.8%) experienced a major bleed or IPTE. The most common IPTE were slow/no reflow (1.5%) and coronary artery dissection with decreased flow (1.1%). Other IPTE occurred in

This work proposes a holistic quantitative snow avalanche risk assessment that evaluates, at reasonable computational costs and for various types of buildings, the impact of forest cover changes on the probability distribution of runout distances, impact pressures and subsequent risk estimates. A typical case study of the French Alps shows that, from a completely deforested to a completely forested path, avalanche risk for a building located downslope decreases by 53–99%, depending on how forest cover is accounted for in avalanche statistical–dynamical modeling. Local forest cover data inferred from old maps and photographs further demonstrates that a 20–60% risk reduction actually occurred between 1825 and 2017 at the site because of the afforestation dynamics, with significant modulations according to the considered building technology. These results (1) assert the protective role of forests against snow avalanches, (2) highlight the potential of combining nature-based solutions with traditional structural measures to reduce risk to acceptable levels at reasonable costs, (3) suggest a significant decrease in risk to settlements in areas that encountered similar forest cover changes and (4) open the door to the quantification of long-term avalanche risk changes as a function of changes of all its hazard, vulnerability and exposure drivers in various mountain context.

The engineered artificial mineral (EnAM) lithium aluminate (LiAlO2) is a promising candidate for the recycling of lithium from slags, which can originate from the reprocessing of batteries, for example. Derivatives of the natural product Punicine (1-(2′,5′-dihydroxyphenyl)-pyridinium) from Punica granatum have been proven to be effective switchable collectors for the flotation of this mineral as they react to light. In the present study, three Punicines were added to a planetary ball mill before grinding LiAlO2 to particle sizes suitable for flotation. We investigated the influence of Punicine and two derivatives with C10 and C17 side chains on the grinding results at different grinding times and conditions as well as on the yields in flotations. SEM images of the particles, IR and ICP–OES measurements provided insights into the Punicine–particle interactions. They showed that Punicines not only prevent the formation of hydrophilic and thus undesirable lithium aluminate hydroxide hydrate (LiAl2(OH)7 ▪ x H2O) surfaces in this process, as is unavoidable in aqueous flotation without this pretreatment, they also prevent the undesired release of lithium cations into the aqueous phase. Due to considerable hydrophobization of the particle surface of LiAlO2, nearly quantitative recovery rates of this engineered artificial mineral are achieved using the process described here.

Inflammation and oxidative stress are implicated in the pathogenesis of Crohn’s disease. Cerium oxide nanoparticle (CNP) conjugated to microRNA 146a (miR146a) (CNP-miR146a) is a novel compound with anti-inflammatory and antioxidative properties. We hypothesized that local administration of CNP-miR146a would improve colitis in a 2,4,6-Trinitrobenzenesulfonic acid (TNBS) mouse model for Crohn’s disease by decreasing colonic inflammation. Balb/c mice were instilled with TNBS enemas to induce colitis. Two days later, the mice received cellulose gel enema, cellulose gel with CNP-miR146a enema, or no treatment. Control mice received initial enemas of 50% ethanol and PBS enemas on day two. The mice were monitored daily for weight loss and clinical disease activity. The mice were euthanized on days two or five to evaluate their miR146a expression, inflammation on histology, and colonic IL-6 and TNF gene expressions and protein concentrations. CNP-miR146a enema successfully increased colonic miR146a expression at 12 h following delivery. At the end of five days from TNBS instillation, the mice treated with CNP-miR146a demonstrated reduced weight loss, improved inflammation scores on histology, and reduced gene expressions and protein concentrations of IL-6 and TNF. The local delivery of CNP-miR146a in a TNBS mouse model of acute Crohn’s colitis dramatically decreased inflammatory signaling, resulting in improved clinical disease.

Background: Advancements in non-ionizing methods for quantifying spinal deformities are crucial for assessing and monitoring scoliosis. In this study, we analyzed the observer variability of a newly developed digital tool for quantifying body asymmetry from clinical photographs. Methods: Prospective observational multicenter study. Initially, a digital tool was developed using image analysis software, calculating quantitative measures of body asymmetry. This tool was integrated into an online platform that exports data to a database. The tool calculated 10 parameters, including angles (shoulder height, axilla height, waist height, right and left waistline angles, and their difference) and surfaces of the left and right hemitrunks (shoulders, waists, pelvises, and total). Subsequently, an online training course on the tool was conducted for twelve observers not involved in its development (six research coordinators and six spine surgeons). Finally, 15 standardized back photographs of adolescent idiopathic scoliosis patients were selected from a multicenter image bank, representing various clinical scenarios (different age, gender, curve type, BMI, and pre- and postoperative images). The 12 observers measured the photographs at two different times with a three-week interval. For the second round, the images were randomly mixed. Inter- and intra-observer variabilities of the measurements were analyzed using intraclass correlation coefficients (ICCs), and reliability was measured by the standard error of measurement (SEM). Group comparisons were made using Student’s t-test. Results: The mean inter-observer ICC for the ten measurements was 0.981, the mean intra-observer ICC was 0.937, and SEM was 0.3–1.3°. The parameter with the strongest inter- and intra-observer validity was the difference in waistline angles 0.994 and 0.974, respectively, while the highest variability was found with the waist height angle 0.963 and 0.845, respectively. No test–retest differences (p > 0.05) were observed between researchers (0.948 ± 0.04) and surgeons (0.925 ± 0.05). Conclusion: We developed a new digital tool integrated into an online platform demonstrating excellent reliability and inter- and intra-observer variabilities for quantifying body asymmetry in scoliosis patients from a simple clinical photograph. The method could be used for assessing and monitoring scoliosis and body asymmetry without radiation.

Waterpipe smoking is frequent in the Middle East and Africa with emerging prevalence worldwide. The epigenome acts as a molecular sensor to exposures and a crucial driver in several diseases. With the widespread use of waterpipe smoking, it is timely to investigate its epigenomic markers and their role in addiction, as a central player in disease prevention and therapeutic strategies. DNA methylome-wide profiling was performed on an exposure-rich population from the Middle East, constituting of 216 blood samples split equally between never, cigarette-only and waterpipe-only smokers. Waterpipe smokers showed predominantly distinct epigenetic markers from cigarette smokers, even though both smoking forms are tobacco-based. Moreover, each smoking form could be accurately (∼90 %) inferred from the DNA methylome using machine learning. Top markers showed dose–response relationship with extent of smoking and were validated using independent technologies and additional samples (total N = 284). Smoking markers were enriched in regulatory regions and several biological pathways, primarily addiction. The epigenetically altered genes were not associated with genetic etiology of tobacco use, and the methylation levels of addiction genes, in particular, were more likely to reverse after smoking cessation. In contrast, other epigenetic markers continued to feature smoking exposure after cessation, which may explain long-term health effects observed in former smokers. This study reports, for the first time, blood epigenome-wide markers of waterpipe smokers and reveals new markers of cigarette smoking, with implications in mechanisms of addiction and the capacity to discriminate between different smoking types. These markers may offer actionable targets to reverse the epigenetic memory of addiction and can guide future prevention strategies for tobacco smoking as the most preventable cause of illnesses worldwide.

We report the case of a 64-year-old man with a history of chemotherapy-induced cardiomyopathy requiring heart transplant in 2022 who underwent successful endomyocardial biopsy using patient-specific computed tomographic fluoroscopic projections. (Level of Difficulty: Beginner.)

IntroductionShorter relative telomere length (RTL) has been associated with increased incidence of morbidity. Although still disputed, available evidence suggests that dietary factors, including sugar-sweetened beverages (SSB) may be linked with shorter RTL. It was argued that the link between SSB and RTL may be explained by the sugar content of these beverages, and specifically fructose given its impact on oxidative stress and the inflammatory response. However, none of the existing studies have examined the specific link between fructose intake and RTL. This exploratory study aimed at (1) assessing the intake of dietary fructose (total, added and natural) in Lebanese healthy adults and (2) examining dietary fructose as a predictor of short telomere length.MethodsFollowing a cross-sectional design (n = 282), anthropometric and biochemical data were collected. RTL was assessed by utilizing real-time polymerase chain reaction (RT-qPCR) to amplify both telomere and single-copy gene segments. Dietary intake was evaluated using a culture-specific food frequency questionnaire (FFQ). Intakes of added fructose, naturally-occurring fructose, and total fructose were estimated.ResultsMean intakes of added and natural fructose were of 39.03 ± 34.12 and 12.28 ± 8.59 g/day, respectively, representing 4.80 ± 3.56 and 1.78 ± 1.41% of total energy intake (EI). Mean total fructose intake was of 51.31 ± 35.55 g/day, contributing 6.58 ± 3.71% EI. Higher intakes of total and added fructose were significantly associated with shorter RTL 2nd RTL tertile as compared to the 3rd RTL tertile; relative risk ratio (RRR) = 3.10 [95% confidence interval (CI): 1.38, 6.94] and RRR = 2.33 (95% CI: 1.02, 5.36), respectively after adjustment for confounders identified using a directed acyclic graph (DAG).ConclusionIn conclusion, although we could not observe a dose-dependent relation between fructose intakes and RTL shortening and although the study is limited by its small sample size, the findings suggest that total and added dietary fructose intakes may be associated with shorter RTL. Larger studies, of longitudinal nature, are needed to further confirm the study findings.

Effective online teaching and learning requires readiness of all stakeholders, students, faculty, and administrators while considering contextual factors that influence the design and delivery of online learning. The purpose of this study is to explore how ready for online teaching faculty are in a Lebanese higher education context and to investigate readiness factors that impact their online teaching. It also aims at identifying any significant differences in readiness based on gender, years of teaching experience and discipline. A survey was developed based on a review of the literature and existing surveys that address readiness factors for online teaching. The survey was administered in Spring 2020, and 210 faculty at a private higher education institution completed the survey. Exploratory Factor Analysis (EFA), Multivariate Analysis of Variance (MANOVA) and descriptive statistics were conducted. The EFA resulted in 5 factors associated with faculty readiness to teach online, namely technology access and skills, course design, online pedagogy, attitude, and institutional support. Descriptive statistics revealed that faculty have the minimum required technology skills to teach online, yet they are faced with technical challenges associated with the context and the need for institutional support. MANOVA tests revealed a statistically significant difference between female faculty members who are readier in terms of course design and attitude than their counterpart males, a statistically significant difference in terms of course design for faculty who have more years of teaching experience. As for discipline specific readiness, majors that are focused on art and design revealed to be less ready for online teaching. This study implies the need for a more robust infrastructure to expand the delivery of online learning in Lebanon and the need for professional development for faculty to create pedagogically and technically enhanced online courses.