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Background: The genus Bartonella is composed of Gram-negative, fastidious, facultative intracellular bacteria that can cause bacteremia in mammals and various disorders in humans. Rodents have been reported as reservoirs of more than 30 Bartonella species, seven of which cause zoonotic infections. Materials and Methods: In the present study, the isolation of Bartonella sp. was attempted from 150 spleen samples from 13 rodent species (mostly Apodemus species) from three geographically different regions in Turkey. Results:Bartonella sp. was successfully isolated from 65 of these 150 samples (43%). The prevalences of Bartonella sp. in tested rodents in the regions of Giresun, Yozgat, and Burdur were 68%, 44%, and 16%, respectively. Using polymerase chain reaction/sequence analysis of the citrate synthase-coding gene (gltA), Bartonellaisolates were classified seven species including B. taylorii, B. grahamii, B. birtlesii, B. mastomydis, and three putatively new Bartonella species. We performed further identification techniques for one of the three Bartonella species that were different from the validated Bartonella species according to the gltA sequence analysis. Conclusion: Here, we report the genomic and phenotypic characterization of Bartonella sp. strain G70 that was isolated from the splenic tissue of an Apodemus uralensis (Pallas 1881), the Ural field mouse, captured in the Giresun region of northeastern Turkey. Bartonella sp. strainG70 (RSKK 22001) was characterized by whole genome and partial gene (gltA, 16S ribosomal RNA) sequencing and comparison, scanning electron microscopy, biochemical tests, and matrix-assisted laser desorption ionization time-of-flight mass spectrometry. This novel Bartonella is a Gram-negative, rod-shaped bacterium and has neither flagella nor pili. The genome from strain G70 was 1,606,969-bp-long with a G + C content of 35.7%. Bartonella rochalimae was found to be the closest phylogenetic relative of strain G70 (OrthoANI = 90.5%, digital DNA–DNA hybridization = 41.4%). We therefore propose that this new species be named Bartonella bilalgolemii sp. nov. with strain G70T as the type strain. [ABSTRACT FROM AUTHOR]

The pyridinium phenolate punicine is a switchable molecule from Punica granatum. Depending on the pH, punicine exists as a cation, neutral molecule, anion, or dianion. In addition, punicine reacts to light, under the influence of which it forms radical species. We report on three punicine derivatives that possess an adamantyl, 2-methylnonyl, or heptadecyl substituent and on their performance in the flotation of lithium aluminate, an engineered artificial mineral (EnAM) for the recycling of lithium, e.g., from lithium-ion batteries. By optimizing the parameters: pH and light conditions (daylight, darkness), recovery rates of 92% of LiAlO2 are achieved. In all cases, the flotation of the gangue material gehlenite (Ca2Al[AlSiO7]) is suppressed. IR, the contact angle, zeta potential measurements, TG-MS, and PXRD confirm that the punicines interact with the surface of LiAlO2, which is covered by LiAl2(OH)7 after contact to water, resulting in a hydrophobization of the particle. The plasma pretreatment of the lithium aluminate has a significant influence on the flotation results and increases the recovery rates of lithium aluminate in blank tests by 58%. The oxidative plasma leads to a partial dehydratisation of the LiAl2(OH)7 and thus to a hydrophobization of the particles, while a reductive plasma causes a more hydrophilic particle surface. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

This report focuses on creating a repository of Benchmark Response (BMR) values sourced from international databases. The objectives included defining BMRs for specific endpoints and considering various characteristics such as compound characteristics, information on the study (e.g. strains, species and gender), information related to toxicity (target organ, type and mechanism of toxicity) and statistical aspects of the dose‐response modelling. The information was retrieved from repositories of risk assessment bodies such as the IRIS‐EPA, JECFA, and OpenFoodTox databases. The methodology section details data acquisition, sources pipeline, and software utilized, ensuring transparency and reproducibility. Techniques like web scraping and text mining complemented manual screening to retrieve and interpret JECFA assessments. OpenFoodTox data served as the reference, involving the filtering for Benchmark Dose (BMD) endpoints and mapping variables for a harmonized setting. When filtering IRIS‐EPA data, the code selected variables based on mapping information and filtered data from multiple sheets, aligning it with the OpenFoodTox reference. Moreover, the post‐processing steps are explained thoroughly, including data import and cleaning. The inventory results in 593 records in a wide format and offers valuable information on BMR values for BMD analysis, facilitating informed decision‐making for relevant future applications. [ABSTRACT FROM AUTHOR]

A well-ventilated room is essential to reduce the risk of airborne transmission. As such, the scientific community sets minimum limits on ventilation with the idea that increased ventilation reduces pathogen concentration and thus reduces the risk of transmission. In contrast, the upper limit on ventilation is usually determined by human comfort and the need to reduce energy consumption. While average pathogen concentration decreases with increased ventilation, local concentration depends on multiple factors and may not follow the same trend, especially within short exposure times over large separation distances. Here, we show through experiments and high-fidelity simulations the existence of a worst-case ventilation where local pathogen concentration increases near the receiving host. This occurs during the type of meetings that were recommended during the pandemic (and in some cases solely authorized) with reduced occupancy adhering to social distancing and short exposure times below 20 minutes. We maintain that for cases of high occupancy and long exposure time, increased ventilation remains necessary. [ABSTRACT FROM AUTHOR]

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. Comprehensive characterization of the glucose-6-phosphate dehydrogenase (G6PD) Meyer variant that contains an R219G substitution suggests compromised dimerization, stability, and catalytic activity of the mutant enzyme causes chronic hemolysis. [ABSTRACT FROM AUTHOR]

The human immunodeficiency virus-1 (HIV-1) nucleocapsid protein (NCp7) is a nucleic acid chaperone protein with two highly conserved zinc fingers. To exert its key roles in the viral cycle, NCp7 interacts with several host proteins. Among them, the human NoL12 protein (hNoL12) was previously identified in genome wide screens as a potential partner of NCp7. hNoL12 is a highly conserved 25 kDa nucleolar RNA-binding protein implicated in the 5'end processing of ribosomal RNA in the nucleolus and thus in the assembly and maturation of ribosomes. In this work, we confirmed the NCp7/hNoL12 interaction in cells by Förster resonance energy transfer visualized by Fluorescence Lifetime Imaging Microscopy and co-immunoprecipitation. The interaction between NCp7 and hNoL12 was found to strongly depend on their both binding to RNA, as shown by the loss of interaction when the cell lysates were pretreated with RNase. Deletion mutants of hNoL12 were tested for their co-immunoprecipitation with NCp7, leading to the identification of the exonuclease domain of hNoL12 as the binding domain for NCp7. Finally, the interaction with hNoL12 was found to be specific of the mature NCp7 and to require NCp7 basic residues. IMPORTANCE: HIV-1 mature nucleocapsid (NCp7) results from the maturation of the Gag precursor in the viral particle and is thus mostly abundant in the first phase of the infection which ends with the genomic viral DNA integration in the cell genome. Most if not all the nucleocapsid partners identified so far are not specific of the mature form. We described here the specific interaction in the nucleolus between NCp7 and the human nucleolar protein 12, a protein implicated in ribosomal RNA maturation and DNA damage response. This interaction takes place in the cell nucleolus, a subcellular compartment where NCp7 accumulates. The absence of binding between hNoL12 and Gag makes hNoL12 one of the few known specific cellular partners of NCp7. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Nontraditional teaching modalities have become the new normal, where hybrid and online education are bound to become an integral component of education at all levels. This paper suggests the coupling of the flipped classroom model with the 5E instructional model for students to develop science understandings and practices in a hybrid and online environment. We demonstrate our model through a middle school unit on animal adaptation and natural selection. In our model, the teacher involves students with asynchronous online activities that raise students' curiosity and help them develop the concepts before the face-to-face or synchronous class activities. The complementary interactive online asynchronous and face-to-face or synchronous activities aim to promote critical thinking and communication on one hand and NGSS Core Ideas and Science Practices on the other. This paper concludes that science teachers can benefit from this model to engage students in inquiry-based activities in both hybrid or remote learning. [ABSTRACT FROM AUTHOR]

The Human Immunodeficiency Virus-1 (HIV-1) nucleocapsid protein (NC) as a mature protein or as a domain of the Gag precursor plays important roles in the early and late phases of the infection. To better understand its roles, we searched for new cellular partners and identified the RNA-binding protein Unr/CSDE1, Upstream of N-ras, whose interaction with Gag and NCp7 was confirmed by co-immunoprecipitation and FRET-FLIM. Unr interaction with Gag was found to be RNA-dependent and mediated by its NC domain. Using a dual luciferase assay, Unr was shown to act as an ITAF (IRES trans-acting factor), increasing the HIV-1 IRES-dependent translation. Point mutations of the HIV-1 IRES in a consensus Unr binding motif were found to alter both the IRES activity and its activation by Unr, suggesting a strong dependence of the IRES on Unr. Interestingly, Unr stimulatory effect is counteracted by NCp7, while Gag increases the Unr-promoted IRES activity, suggesting a differential Unr effect on the early and late phases of viral infection. Finally, knockdown of Unr in HeLa cells leads to a decrease in infection by a non-replicative lentivector, proving its functional implication in the early phase of viral infection. [ABSTRACT FROM AUTHOR]

While significant advances have been made in pharmacogenetics (PGx), especially in countries with developed economies, this field remains at its infancy in developing countries and low resource environments. Herein, we provide insights into the gap and challenges of PGx at the research and clinical fronts, and some perspectives to bridge the gap and move forward with PGx in the developing world. We show that developing countries fall behind in PGx research, evidenced by a lower number of researchers, citations, and research output. In addition, the implementation of PGx in the clinic has been progressing at a much slower pace than research, and more so in developing countries. To bridge this gap, we recommend fostering regional and multinational collaborations to secure funds for high-throughput genotyping and local capacity building while preserving individual countries' identity, implementing next-generation sequencing, and organizing specialized training and exchange programs to move PGx research and clinical applications forward in developing countries. [ABSTRACT FROM AUTHOR]

Strain Marseille-P9829 was isolated from a bone sample collected from an open right fibula fracture from a 46-years old patient. Strain Marseille-P9829 (= CSUR P9829 = DSM 110695) was a Gram-negative, non-spore-forming and non-motile bacterium. This strain had a positive catalase activity but was oxidase-negative. The major fatty acids methyl esters were hexadecanoic acid (45.6%) and 9-hexadecenoic acid (28.4%). Matrix Assisted Laser Desorption/Ionization-Time of Flight Mass Spectrometry analysis suggested that this strain belongs to the species Buttiauxella gaviniae. Since there were few reports of clinical infections with this species in humans, whole genome sequencing was performed and a polyphasic taxono-genomic approach was followed in order to verify the classification of strain Marseille-P9829. The 16S rRNA gene sequence BLAST against the NCBI database yielded the highest similarity of 99.8% with Buttiauxella agrestis, suggesting that strain Marseille-P9829 belongs to this species. However, genomic comparison by digital DNA–DNA hybridization showed that values between strain Marseille-P9829 and other validly published Buttiauxella species were all lower than 70%. Furthermore, all average nucleotide identities were lower than 95–96%. Therefore, these results confirmed that strain Marseille-P9829 belonged to a new Buttiauxella species for which we propose the name Buttiauxella massiliensis sp. nov., with strain Marseille-P9829 as type strain. [ABSTRACT FROM AUTHOR]

Strains Marseille-P2265T (=CSUR P2265T =DSM 102082 T) and Marseille-P3890T (=CSUR P3890T =CCUG 72341 T) were isolated from stool samples using the culturomics approach. The 16S rRNA gene sequences of both strains were sequenced and compared by BLASTn to the NCBI database. Strains Marseille-P2265T and Marseille-P3890T were most closely related to Acutalibacter muris with identities of 94.3% and 91.5%, respectively. Between the two strains, the 16S rRNA gene sequence identity was 91.5%. Both strains are anaerobic Gram-positive, oxidase- and catalase-negative. The major fatty acid methyl esters (> 10%) in both strains are C16:0 and anteiso-C15:0. Additionally, strain Marseille-P2265T has iso-C15:0 and C14:0, and strain Marseille-P3890T, iso-C14:0. Strain Marseille-P2265T has a genome size of 3,671,396-bp with a G + C content of 52.8%. As for strain Marseille-P3890T, the genome is 2,702,024-bp-long with a 39.8% G + C content. The genomic comparison of closely related species with strains Marseille-P2265T and Marseille-P3890T showed that all digital DNA-DNA hybridization (dDDH), orthologous average nucleotide identity (OrthoANI) and average amino acid identity (AAI) values were lower than the published species thresholds (70% for dDDH, 95–96% for OrthoANI/AAI). Based on these results, it was concluded that strains Marseille-P2265T and Marseille-P3890T belong to two new genera in the family Oscillospiraceae. For these two genera, the names Neglectibacter gen. nov. and Scatolibacter gen. nov. were proposed, with strains Marseille-P2265T and Marseille-P3890T being the type strains of Neglectibacter timonensis gen. nov., sp. nov. and Scatolibacter rhodanostii gen. nov., sp. nov., respectively. [ABSTRACT FROM AUTHOR]

Secondary ion mass spectroscopy, Fourier transformed infrared spectroscopy, ellipsometry, reflection high energy diffraction and transmission electron microscopy are used to gain inside into the effect of Ge on the formation of ultrathin 3C‐SiC layers on Si(111) substrates. Accompanying the experimental investigations with simulations it is found that the ultrathin single crystalline 3C‐SiC layer is formed on top of a gradient Si1–x–yGexCy buffer layer due to a complex alloying and alloy decomposition processes promoted by carbon and germanium interdiffusion and SiC nucleation. This approach allows tuning residual stress at very early growth stages as well as the interface properties of the 3C‐SiC/Si heterostructure. Useful yields of secondary ions of Ge in Si matrix and Si dimer are estimated. [ABSTRACT FROM AUTHOR]

Introduction: The forced transition to online learning due to the COVID-19 pandemic has impacted medical education significantly. Methods: In this paper, the authors compare the performance of Year 1 and 2 classes of medical students who took the same courses either online (2019-2020) or face-to-face (2018-2019), and compare their evaluation of these courses. The authors also present results of three survey questions delivered to current Year 1 medical students on the perceived advantages and disadvantages of online learning and suggestions for improvement. Results: Performance and evaluation scores of Year 1 and 2 classes was similar irrespective of the mode of delivery of the course in question. 30 current (2019-2020) Year 1 students responded to the survey questions with a response rate of 25.4%. Some of the cited disadvantages had to do with technical, infrastructural and faculty know-how and support. But the more challenging limitations had to do with the process of learning and what facilitates it, the students' ability to self-regulate and to motivate themselves, the negative impact of isolation, loss of socialisation and interaction with peers and faculty, and the almost total lack of hands-on experiences. Conclusion: Rapid transition to online learning did not affect student knowledge acquisition negatively. As such, the sudden shift to online education might not be a totally negative development and can be harnessed to drive a more progressive medical education agenda. These results are particularly important considering the several disadvantages that the students cited in relation to the online delivery of the courses. [ABSTRACT FROM AUTHOR]

Background: Screening for lung cancer with low‐dose computed tomography (LDCT) was shown to reduce lung cancer incidence and overall mortality, and it has been recently included in international guidelines. Despite the rising burden of lung cancer in low and middle‐income countries (LMICs) such as Lebanon, little is known about what primary care physicians or pulmonologists know and think about LDCT as a screening procedure for lung cancer, and if they recommend it. Objectives: Evaluate the knowledge about LDCT and implementation of international guidelines for lung cancer screening among Lebanese primary care physicians (PCPs) and pulmonary specialists. Methodology: PCPs and PUs based in Lebanon were surveyed concerning knowledge and practices related to lung cancer screening by self‐administered paper questionnaires. Results: 73.8% of PCPs and 60.7% of pulmonary specialists recognized LDCT as an effective tool for lung cancer screening, with 63.6% of PCPs and 71% of pulmonary specialists having used it for screening. However, only 23.4% of PCPs and 14.5% of pulmonary specialists recognized the eligibility criteria for screening. Chest X‐ray was recognized as ineffective by only 55.8% of PCPs and 40.7% of pulmonary specialists; indeed, 30.2% of PCPs and 46% of pulmonary specialists continue using it for screening. The majority have initiated a discussion about the risks and benefits of lung cancer screening. Conclusion: PCPs and pulmonary specialists are initiating discussions and ordering LDCT for lung cancer screening. However, a significant proportion of both specialties are still using a non‐recommended screening tool (chest x‐ray); only few PCPs and pulmonary specialists recognized the population at risk for which screening is recommended. Targeted provider education is needed to close the knowledge gap and promote proper implementation of guidelines for lung cancer screening. [ABSTRACT FROM AUTHOR]

BACKGROUND: The role of urine studies in the detection of urinary tract infection (UTI) in febrile neutropenic patients with urinary symptoms (having a urinary catheter or having a positive urine analysis) is inarguable. However, the evidence is scarce regarding the indication for urine studies in asymptomatic (i.e., without urinary symptoms) patients with febrile neutropenia (FN) presenting to the emergency department (ED). The aim of this study is to evaluate the need for obtaining urine studies in asymptomatic febrile neutropenic patients. METHODS: This was a retrospective cohort study conducted on adult cancer patients who presented to the ED with FN and had no urinary symptoms. We included all ED presentations of eligible patients between January 2013 and September 2018. Student's t-test and Wilcoxon rank-sum test were used for continuous data, while Chi-square and Fisher's exact tests were used for categorical data. Participants were divided into two groups based on their urine culture (UC) results: negative and positive UCs. Two cut-off s were used for positive UC results: =105 cfu/mL and =104 cfu/mL. RESULTS: We included 284 patients in our study. The age of our patient population was 48.5±18.5 years. More than two-thirds (68.7%) of patients had severe neutropenia, while only 3.9% and 9.9% of the patients had positive UCs at =105 cfu/mL and =104 cfu/mL, respectively. UCs were expectedly positive in most patients with urinalysis (UA) abnormalities. However, 27.3% and 32.1% of patients with positive UCs at =105 cfu/mL and =104 cfu/mL respectively had a normal UA. CONCLUSIONS: In our study, the incidence of UTI in adult febrile neutropenic cancer patients who present to the ED without urinary symptoms is low. Consequently, routine urine testing may not be warranted in this population, as it adds unnecessary financial burdens on the patients and delays timely management. [ABSTRACT FROM AUTHOR]

Hearing aid and cochlear implant (CI) users often struggle to locate and segregate sounds. The dominant sound-localisation cues are time and intensity differences across the ears. A recent study showed that CI users locate sounds substantially better when these cues are provided through haptic stimulation on each wrist. However, the sensitivity of the wrists to these cues and the robustness of this sensitivity to aging is unknown. The current study showed that time difference sensitivity is much poorer across the wrists than across the ears and declines with age. In contrast, high sensitivity to across-wrist intensity differences was found that was robust to aging. This high sensitivity was observed across a range of stimulation intensities for both amplitude modulated and unmodulated sinusoids and matched across-ear intensity difference sensitivity for normal-hearing individuals. Furthermore, the usable dynamic range for haptic stimulation on the wrists was found to be around four times larger than for CIs. These findings suggest that high-precision haptic sound-localisation can be achieved, which could aid many hearing-impaired listeners. Furthermore, the finding that high-fidelity across-wrist intensity information can be transferred could be exploited in human–machine interfaces to enhance virtual reality and improve remote control of military, medical, or research robots. [ABSTRACT FROM AUTHOR]

Essential oils of three Lebanese Rose species (Rosa corymbifera Borkh., Rosa Phoenicia Boiss. and Rosa damascena Mill.) were investigated, to assess their bioactive components after hydrodistillation, using a Clevenger-type apparatus. A GC/MS analysis of the oil content of Rose species led to the identification of 22, 46 and 30 components in each of R. damascena, R. corymbifera and R. Phoenicia, respectively, representing 83.4 %, 72.9 % and 84.7 % of the total EO of the corresponding Rose species. The EOs chemical profile analysis showed that the main components of R. corymbifera (heptacosane (14.8 %), tricosane (10.6 %), pentacosane (8.6 %), nonacosane (8.6 %) and heneicosane (5.6 %)) and of R. Phoenicia (heptacosane (17.1 %), tricosane (12.9 %), heneicosane (12.3 %), docosane (12.1 %) and cycloeicosane (7.6 %)) were hydrocarbons. While hydro- carbons were also identified in R. damascena (nonadecane (12.4 %) and heneicosane (8.1 %)), they were not its most abundant constituents. The major component of R. damascena was phenethyl alcohol (28.5 %), a benzenoid compound, also identified in R. phoenicia (5.1 %). Moreover, an oxygenated terpene (β-citronellol (13.2 %)) was also identified in R. damascena. Since R. damascena is largely cultivated in Lebanon, a comparative study of R. damascena EO was performed on a group of samples collected from different locations (ours and data previously published), to identify the presence of any chemical polymorphism according to the geographical location. GC/ MS analysis together with principal component analysis (PCA) highlighted six different chemotypes for R. damascena EO: citronellol, geraniol, nerol, nonadecane, phenyl ethyl alcohol and heneicosane. This chemical variability suggests the involvement of abiotic and biotic factors that need to be further investigated. [ABSTRACT FROM AUTHOR]

Objective: The American University of Beirut Faculty of Medicine follows the American model of medical education. In 2013-2014, a carefully designed new curriculum replaced the previous, largely traditional curriculum, and aimed to improve student wellbeing, upgrade the learning environment, enhance student empathy, and counter the negative influences of the hidden curriculum. This longitudinal study assessed the effectiveness of the new curriculum in those domains over a period of 7 years. Methods: Three cohorts of medical students anonymously filled a paper-based survey at the end of years 1, 2, 3, and 4 of the 4-year curriculum. These included the Class of 2016, the last batch of students who followed the old curriculum, and 2 cohorts that followed the new curriculum (Class of 2017 and Class of 2019). The perceived learning environment was assessed by the Dundee Ready Education Environment Measurement survey; the student's empathy was assessed by the Jefferson Scale of Physician Empathy-Student version; and the hidden curriculum was examined using a locally developed survey. Results: The scores on the learning environment survey were significantly higher among the cohorts following the new curriculum relative to those following the old curriculum. Similar significant results appeared when looking at each of the subscales for the learning environment. The students' empathy scores were also significantly higher in both cohorts of the new curriculum when compared with the old curriculum. Nevertheless, there was a significant decrease in empathy in both third and fourth years relative to second year. The new curriculum also improved aspects of the students' perceptions and responses to the hidden curriculum. Conclusion: In conclusion, a well-planned and well-researched curricular intervention, based on sound educational theories, practices, and standards can indeed transform the learning environment, as well as the attitudes, values, and experiences of medical students. [ABSTRACT FROM AUTHOR]

Ridesourcing (Uber, Careem, Lyft, ...) is emerging as a main player in the transportation industry. However, its relation to mass transit remains ambiguous, with divided opinions on its complementarity or substitutive effect towards high capacity public transportation systems. This study examines the integration of ridesourcing and transit, particularly focusing on modeling the demand for mass transit when ridesourcing is used as an access or egress mode to mass transit. It extends the existing literature on the integration of transit and new mobility concepts by providing a modeling framework that incorporates all stages of multi-modal trips such as those that involve using mass transit. A mixed logit with error component structure is presented to capture correlations in unobserved factors across multi-modal alternatives sharing similar modes at certain stages. The framework incorporates uni-modal and multi-modal travel alternatives and distinguishes between access, main mode, and egress stages without applying constraints on possible combinations. An application to Beirut's planned Bus Rapid Transit (BRT) system, performed on a data set of 392 respondents, reveals that ridesourcing as a feeder mode is mostly popular with young commuters while also being perceived as more reliable than feeder buses and jitneys. Awareness and familiarity are major drivers for the service implying higher potential in the future. A complementarity effect with transit is found as the introduction of ridesourcing at the feeders' level is expected to drive an additional 2% of commuters to use the BRT. Decreasing ridesourcing fare is effective for its integration with transit, as a fare decrease of 50% increases BRT market share from 33.53% to 36.89% of all motorized trips, implying possible synergies between the two modes. Forecasting results further reveal that additional taxes on parking used by car commuters and increasing park and ride capacity at BRT stations are effective policies to augment BRT ridership. [ABSTRACT FROM AUTHOR]

To evaluate polymorphisms in genes of drug metabolizing enzymes and transporters involved in cyclosporine and/or voriconazole disposition among patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT). DNA from forty patients was genotyped using the DMETPlus array. The average ratio of cyclosporine concentration/dose (C/D in (ng/mL)/(mg/kg)) per participant's weight was computed using available trough levels and daily doses. The C/D cyclosporine ratio was significantly higher when it was administered with voriconazole as compared to when it was administered alone: median: 116.75 vs. 25.40 (ng/mL)/(mg/kg) with and without voriconazole respectively, (P < 0.001). There was also a significant association between the C/D cyclosporine ratio combined with voriconazole and the ABCB1 2677 G > T > A (rs2032582) genetic polymorphism (P = 0.05). In parallel, ABCB1 variant allele carriers had higher creatinine in combination therapy with a median creatinine (mg/dL) of 0.74 vs. 0.56 for variant allele carriers vs. reference; P = 0.003. Interestingly, CYP2C9, CYP2C19, and CYP3A5 extensive metabolizers tended to be associated with lower cyclosporine C/D ratio when combined with voriconazole, but the results were not statistically significant. To the best of our knowledge, this is the first pharmacogenetic study on the interaction between voriconazole and cyclosporine in patients undergoing allo-HCT. Results suggest that the ABCB1 2677 G > T > A genetic polymorphism plays a role in this interaction with cyclosporine related nephrotoxicity. Pre-emptive genotyping for this genetic variant may be warranted for cyclosporine dose optimization. Larger studies are needed to potentially show significant associations with more candidate genes such as CYP3A4/5, CYP2C9, and CYP2C19 , among others. [ABSTRACT FROM AUTHOR]

We present results from direct numerical simulations on laminar and turbulent non-canonical thermals with an initial rectangular density distribution at a Reynolds number of Re = 500 and Re = 5000, respectively. We find the non-canonical shape to induce strong azimuthal variations in the thermal for both the laminar and turbulent cases. These include noticeable differences in downward and horizontal propagation speeds as well as differences in the strength of the vortex tube. These differences persist over a significant period of time and help generate a cross-flow component that is otherwise not present in canonical cases. The cross-flow component is in the opposite direction to that observed in gravity currents with the same initial density distribution. This is counterintuitive seeing that both flows are solely driven by buoyancy. By extracting the three-dimensional streamlines, we find the descending vortex tube to force the dense fluid to follow a helical path. [ABSTRACT FROM AUTHOR]

Objective: The American University of Beirut Faculty of Medicine follows the American model of medical education. In 2013-2014, a carefully designed new curriculum replaced the previous, largely traditional curriculum, and aimed to improve student wellbeing, upgrade the learning environment, enhance student empathy, and counter the negative influences of the hidden curriculum. This longitudinal study assessed the effectiveness of the new curriculum in those domains over a period of 7 years. Methods: Three cohorts of medical students anonymously filled a paper-based survey at the end of years 1, 2, 3, and 4 of the 4-year curriculum. These included the Class of 2016, the last batch of students who followed the old curriculum, and 2 cohorts that followed the new curriculum (Class of 2017 and Class of 2019). The perceived learning environment was assessed by the Dundee Ready Education Environment Measurement survey; the student's empathy was assessed by the Jefferson Scale of Physician Empathy-Student version; and the hidden curriculum was examined using a locally developed survey. Results: The scores on the learning environment survey were significantly higher among the cohorts following the new curriculum relative to those following the old curriculum. Similar significant results appeared when looking at each of the subscales for the learning environment. The students' empathy scores were also significantly higher in both cohorts of the new curriculum when compared with the old curriculum. Nevertheless, there was a significant decrease in empathy in both third and fourth years relative to second year. The new curriculum also improved aspects of the students' perceptions and responses to the hidden curriculum. Conclusion: In conclusion, a well-planned and well-researched curricular intervention, based on sound educational theories, practices, and standards can indeed transform the learning environment, as well as the attitudes, values, and experiences of medical students. [ABSTRACT FROM AUTHOR]

We present results from direct numerical simulation on the transition from straight‐crested to sinuous‐crested bedforms. The numerical setup is representative of turbulent open channel flow over an erodible sediment bed at a shear Reynolds number of Reτ = 180. The immersed boundary method accounts for the presence of the bed. The simulations are two‐way coupled such that the turbulent flow can erode and modify the bed, and in turn, the bed modifies the overlying flow. Coupling from the flow to the bed occurs through the Exner equation, while back coupling from the bed to the flow is achieved by imposing the no‐slip and no‐penetration condition at the immersed boundary. The simulation setup is similar to that by Zgheib et al. (2018a, https://doi.org/10.1002/2017JF004398) except for the presence of sidewalls to better mimic laboratory flume conditions. Sidewalls are observed to significantly increase bedform sinuosity. Key Points: Lateral sidewalls significantly increase crestline sinuosityInfluence of lateral domain extent on sinuosity is small but noticeableInfluence of lateral extent is amplified in the presence of sidewalls [ABSTRACT FROM AUTHOR]

Introduction: Lebanon lacks a national database of gunshot injuries (GSIs), which limits injury prevention initiatives. Objectives: This study examines patient characteristics, injury patterns, and clinical outcomes in GSI victims and evaluates the impact of intent on clinical outcomes with the aim of improving awareness among emergency department (ED) physicians about the importance of inquiring about intent to predict prognosis. Materials and Methods: We conducted a retrospective cohort study of GSI victims presenting to the ED of a tertiary care center in Beirut, Lebanon. Descriptive and bivariate analyses were done to identify differences based on intent. Results: A total of 83 patients were included, 59% with intentional GSI, 22% with unintentional GSI, and 19% with unspecified intent. They were mostly males (89.2%), with a mean age of 31.7 years, and mostly presenting during summer seasons. Females were more commonly victims of unintentional GSI. All victims sustaining multiple GSIs were in the intentional group. When compared to unintentional GSI, intentional and unspecified GSIs were found to result in more ICU admissions (46.9%, 31.3%, and 16.7%,P = 0.096), significantly longer hospital stays (18.2, 26.3, and 5.6 days;P = 0.001) and higher mortality (11.6%, 18.2%, and 6.7%;P = 0.747). The rates of surgical procedures were similar between the three groups although more victims of intentional and unspecified GSI underwent multiple surgeries. Conclusion: GSIs have different features, resource utilization, and clinical outcomes depending on the intentionality of injuries. All GSI victims suffer from substantial morbidity and mortality, but intentionally harmed victims sustain more severe injuries with worse outcomes. [ABSTRACT FROM AUTHOR]

We present results on the formation of ripples from linear stability analysis. The analysis is coupled with direct numerical simulations of turbulent open-channel flow over a fixed sinusoidal bed. The presence of the sediment bed is accounted for using the immersed boundary method. The simulations are used to extract the bed shear stress and consequently the sediment transport rate. The approach is different from traditional linear stability analysis in the sense that the phase lag between the bed topology and the sediment flux is obtained from the three-dimensional turbulent simulations. The stability analysis is performed on the Exner equation, whose input, the sediment flux, is provided from the simulations. We ran 11 simulations at a fixed shear Reynolds number of 180, but for different sediment bed wavelengths. The analysis allows us to sweep a large range of physical and modelling parameters to predict their effects on linear growth. The Froude number appears to be the critical controlling parameter in the early linear development of ripples, in contrast with the dominant role of particle Reynolds number during the equilibrium stage. We also present results from a wave packet analysis using a one-dimensional Gaussian ridge. [ABSTRACT FROM AUTHOR]

Salvia fruticosaa perennial aromatic plant, endemic to the Mediterranean region, is the most used medicinal plant in Lebanon. S. fruticosa essential oils (EOs) are widely acknowledged in the Lebanese traditional medicine to treat several ailments. Plant samples were harvested at various months of the year 2013, from 4 different Lebanese areas: Baabda, Ansariyeh, Harissa and Nahr Ibrahim. Fresh herb was either air dried or lyophilized. EOs were obtained using 2 extraction techniques: Solvent-Free Microwave Extraction (SFME) and conventional hydro distillation. The chemical variability of Lebanese S. fruticosa EO quantity and quality was assessed according to harvesting time and region, drying methods and EO extraction techniques. GC/MS showed that the major compounds in the oils were: eucalyptol (18.3-83.7 %), trans-anethole (0.00-61.7 %), β-caryophyllene (0.00-38 %), and camphor (0.00-16.7 %). EO yields were affected by plant's growth stages, drying methods and EO extraction techniques. EO extraction methods and harvesting time and region had an impact on EO chemical composition whereas tested drying methods had no significant influence. Our study highlighted 4 different chemotypes for S. fruticosa EO: eucalyptol, camphor, α-thujoneand trans-anethole. For the first time in our study, trans-anethole was found as distinguishable chemotype. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has forced changes in the delivery of medical education. We aimed to explore these changes and determine whether they will impact the future of medical education in any way. We invited leaders in medical education from all accessible US-based medical schools to participate in an online individual semi-structured interview. Representatives of 16 medical schools participated. They commented on the adequacy of online education for knowledge transfer, and the logistical advantages it offered, but decried its negative influence on social learning, interpersonal relationships and professional development of students, and its ineffectiveness for clinical education. Most participants indicated that they would maintain online learning for didactic purposes in the context of flipped classrooms but that a return to in-person education was essential for most other educational goals. Novel content will be introduced, especially in telemedicine and social medicine, and the students' roles and responsibilities in patient care and in curricular development may evolve in the future. This study is the first to document the practical steps that will be adopted by US medical schools in delivering medical education, which were prompted and reinforced by their experience during the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Background: Diabetic wounds have become one of the most challenging public health issues of the 21st century, yet there is no effective treatment available. We have previously shown that the diabetic wound healing impairment is associated with increased inflammation and decreased expression of the regulatory microRNA miR-146a. We have conjugated miR-146a to cerium oxide nanoparticles (CNP-miR146a) to target reactive oxygen species (ROS) and inflammation. This study aimed to evaluate the consequences of CNP-miR146a treatment of diabetic wounds.Study Design: Eight-millimeter wounds were created on the dorsal skin of Db/Db mice and treated with PBS or differing concentrations of CNP-mir146a (1; 10; 100; or 1,000 ng) at the time of wounding. Rate of wound closure was measured until the wounds were fully healed. At 4 weeks post-healing, a dumbbell-shaped skin sample was collected, with the healed wound in the center, and an Instron 5942 testing unit was used to measure the maximum load and modulus.Results: Our data showed that diabetic wounds treated with PBS or 1 ng CNP-miR146a took 18 days to heal. Treatment with 10, 100, or 1,000 ng of CNP+miR-146a effectively enhanced healing, and wounds were fully closed at day 14 post-wounding. The healed skin from the CNP-miR146a-treated group showed a trend of improved biomechanical properties (increased maximum load and modulus), however it did not reach significance.Conclusions: We found that a 100-ng dose of CNP-miR146a improved diabetic wound healing and did not impair the biomechanical properties of the skin post-healing. This nanotechnology-based therapy is promising, and future studies are warranted to transfer this therapy to clinical application. [ABSTRACT FROM AUTHOR]

Objective: To study the functional outcome of patients undergoing transurethral enucleation and resection of the prostate (TUERP) vs patients undergoing holmium laser enucleation of the prostate (HoLEP) in men with bladder outlet obstruction. Materials and Methods: We retrospectively analyzed our prospectively collected database of two groups of patients. Twenty-four patients underwent TUERP (group 1), and 27 underwent HoLEP (group 2). Preoperative characteristics, intervention parameters, postoperative functional outcomes, uroflowmetry, and complications were collected. Results: Mean prostate size in groups 1 and 2 were 87.2 and 93.5 cc, respectively. The mean duration of surgery was 110 minutes in group 1 and 136 minutes in group 2. In group 1, prostate-specific antigen (PSA) dropped from 4.4 to 1.2 ng/cc after 12 months. International Prostate Symptom Score (IPSS) was 3.75 at 12 months with a preoperative value of 20.9. With respect to maximum urinary flow rate (Qmax), it increased to 21.8 mL/s from a preoperative value of 6.4 mL/s. In group 2, the PSA dropped from 7.6 to 1.3 ng/cc. IPSS dropped from 22.3 to 3.8, Qmax increased from 7.7 to 22.5 mL/s. Hemoglobin, complications, and all studied parameters were not statistically significant between both groups. Conclusion: In this study, TUERP was safe and efficacious in benign prostatic hyperplasia patients with large glands. Modifications can be implemented on the standard transurethral resection of the prostate technique to treat patients with prostate sizes >70 cc. [ABSTRACT FROM AUTHOR]

The behaviour of concrete structures is affected by the time-dependent volume changes of concrete caused by sustained loads and moisture loss. Creep deformations have an important effect on long-term integrity of reinforced concrete structures. Incorrect or inaccurate prediction of these volume changes leads to undesirable and harmful consequences for the structures. Knowing that the Eurocode 2 does not take admixtures and additives into consideration in predicting creep deformations, the aim of this study is to apply correction coefficients to the Eurocode 2 creep formulas to take into account the effect of additives and admixtures, especially silica fume and water reducer. A large database from international laboratories and research centres is used in this study. The first step consists of comparing experimental measurements of creep deformations with creep values predicted by the Eurocode 2 formulas. The second step lies in introducing correction coefficients to the creep formulas of Eurocode 2, taking into consideration the percentage of admixtures and additives. These new correction coefficients are introduced in the Eurocode 2 formulas using an approximate Bayesian computation method based on a rejection algorithm. [ABSTRACT FROM AUTHOR]

Physical attacks are powerful threats that can cause changes in the execution behavior of a program. Control-Flow Integrity (CFI) is used to check the program's flow execution, ensuring that it remains unaltered by these attacks. The RISC-V Trace Encoder (TE) provides valuable information about the user program's execution path, and is used as part of a CFI solution. An enhanced version of the TE specifications permits detecting intricate fault models such as the corruption of any discontinuity instruction, using an additional Trace Verifier (TV) hardware module. In this paper, we present a buffer overflow software attack simulation and experimental ElectroMagnetic Fault Injection (EMFI) attacks conducted on an Field Programmable Gate Array (FPGA) board that implements a RISC-V core linked to the enhanced TE and TV modules. Unlike existing CFI solutions, our proposed approach does not require modifications to the RISC-V compiler, user application code or the RISC-V core. The average overhead of our solution in terms of hardware area, memory and power consumption are equal to 13.6%, 3.5% and 9% respectively. [ABSTRACT FROM AUTHOR]

In Lebanon, data stemming from national cross-sectional surveys indicated significant increasing trends in the prevalence of cardiovascular diseases and associated behavioral and age-related risk factors. To our knowledge, no data are available on relative telomere length (RTL) as a potential biomarker for age-related diseases in a Lebanese population. The aim of this study was to evaluate whether there is an association between RTL and demographic characteristics, lifestyle habits and diseases in the Lebanese. This was a cross-sectional study of 497 Lebanese subjects. Peripheral blood RTL was measured by amplifying telomere and single copy gene using real-time PCR. Mean ± SD RTL was 1.42 ± 0.83, and it was categorized into 3 tertiles. Older age (P=0.002) and wider waist circumference (WC) (P=0.001) were statistically significantly associated with shorter RTL. Multinomial logistic regression showed that subjects who had some level of sleeping difficulty had a statistically significantly shorter RTL when compared to those with no sleeping difficulties at all [OR (95% CI): 2.01 (1.11-3.62) in the first RTL tertile]. Importantly, statistically significantly shorter RTL was found with every additional 10 cm of WC [OR (95% CI): 1.30 (1.11-1.52) for first RTL tertile]. In addition, and after performing the multivariate logistic regression and adjusting for "predictors" of RTL, the odds of having hypertension or being treated for hypertension were higher in patients who had shorter RTL: OR (95% CI): 2.45 (1.36-4.44) and 2.28 (1.22-4.26) in the first RTL tertiles respectively with a similar trend, though not statistically significant, in the second RTL tertiles. This is the first study in Lebanon to show an association between age, central obesity, poor sleep and hypertension and RTL. It is hoped that telomere length measurement be potentially used as a biomarker for biological age and age-related diseases and progression in the Lebanese. [ABSTRACT FROM AUTHOR]

Impaired diabetic wound healing is associated with a dermal extracellular matrix protein profile favoring proteolysis; within the healing diabetic wound, this is represented by an increase in activated matrix metalloproteinase (MMPs). Treatment of diabetic wounds with mesenchymal stem cells (MSCs) has been shown to improve wound healing; however, there has not yet been an assessment of their ability to correct dysregulation of MMPs in diabetic wounds. Furthermore, there has been no prior assessment of the role of microRNA29b (miR-29b), an inhibitory regulatory molecule that targets MMP-9 mRNA. Using in vitro models of fibroblast coculture with MSCs and in vivo murine wound healing models, we tested the hypothesis that MSCs correct dysregulation of MMPs in a microRNA-29b-dependent mechanism. In this study, we first demonstrated that collagen I and III protein content is significantly reduced in diabetic wounds, and treatment with MSCs significantly improves collagen I content in both nondiabetic and diabetic wounds. We then found that MMP-9 gene expression and protein content were significantly upregulated in diabetic wounds, indicating elevated proteolysis. Treatment with MSCs resulted in a decrease in MMP-9 gene expression and protein content level in diabetic wounds 3 and 7 days after wounding. Zymographic analysis indicated that MSC treatment also decreased the amount of activated MMP-9 present in diabetic wounds. Furthermore, miR-29b expression was inversely associated with MMP-9 gene expression; miR-29b expression was decreased in diabetic wounds and diabetic fibroblast. Following treatment of diabetic wounds with MSCs, as well as in diabetic fibroblasts cocultured with MSCs, miR-29b was significantly increased. These findings suggest a potential mechanism through which MSCs enhance diabetic wound healing by improving collagen I content in diabetic wounds through decreasing MMP-9 expression and increasing miR-29b expression. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus is a complex, systemic metabolic disease characterized by insulin resistance and resulting hyperglycemia, which is associated with impaired wound healing. The clinical complications associated with hyperglycemia are attributed, in part, to the increased production of reactive oxygen species (ROS). Recent studies revealed that long non-coding RNAs (lncRNAs) play important regulatory roles in many biological processes. Specifically, lncRNA Lethe has been described as exhibiting an anti-inflammatory effect by binding to the p65 subunit of NFκB and blocking its binding to DNA and the subsequent activation of downstream genes. We therefore hypothesize that dysregulation of Lethe’s expression plays a role in hyperglycemia-induced ROS production. To test our hypothesis, we treated RAW264.7 macrophages with low glucose (5 mM) or high glucose (25 mM) for 24h. High glucose conditions significantly induced ROS production and NOX2 gene expression in RAW cells, while significantly decreasing Lethe gene expression. Overexpression of Lethe in RAW cells eliminated the increased ROS production induced by high glucose conditions, while also attenuating the upregulation of NOX2 expression. Similar results was found also in non-diabetic and diabetic primary macrophage, bone marrow derived macrophage (BMM). Furthermore, overexpression of Lethe in RAW cells treated with high glucose significantly reduced the translocation of p65-NFkB to the nucleus, which resulted in decreased NOX2 expression and ROS production. Interestingly, these findings are consistent with the decreased Lethe gene expression and increased NOX2 gene expression observed in a mouse model of diabetic wound healing. These findings provide the first evidence that lncRNA Lethe is involved in the regulation of ROS production in macrophages through modulation of NOX2 gene expression via NFκB signaling. Moreover, this is the first report to describe a role of lncRNAs, in particular Lethe, in impaired diabetic wound healing. Further studies are warranted to determine if correction of Lethe expression in diabetic wounds could improve healing. [ABSTRACT FROM AUTHOR]

In France, residential wood heating represents 52% of the share of energy produced from renewable resources for heat production. The forest of the Grand Est region (FR) covers one third of the regional territory and 12% of the national forest area. The main purpose of this study is to assess and to compare the global warming and the human health effects of the wood energy sector at domestic and regional scales. Five scenarios systems were studied. S1 (wood-log scenario and S2 (pellet scenario) were compared in real conditions of use. S3 studies in details the pellet manufacturing process. The novelty of the study compares S1 and S2 at the regional scale with two new scenarios S4 and S5 considering the entire log inserts and pellets stoves listed in the region. A cradle-to-grave approach was applied including all stages from forestry operations to heat production by combustion. Scenario S2 leads to a higher global change than S1 with values of 73.7 and 44.1 kg CO 2 eq per ton of green wood, respectively. If the combustion stage of pellets emits less greenhouse gases than the combustion of logs, the stage production contributes for 67% of the total impact. The packaging was the main process having the highest health and environmental impacts. At regional scale, the combustion stage mainly enhances all impacts due to the presence of old appliances with low environmental efficiency. Public policies must continue their efforts to promote the replacement of old household appliances. • Combustion of wood logs produces 6 times more greenhouse gases than wood pellets at domestic scale. • The production of pellets has significant health and environmental impacts. • The packaging of pellets isresponsible for carcinogenic, non-carcinogenic, respiratory organic and climate change. • The use of old domestic appliances at a regional scale multiplies the effects of the combustion process on all impacts. [ABSTRACT FROM AUTHOR]

We previously showed that oxidative stress inhibits leukemia inhibitory factor (LIF) signaling by targeting JAK1, and the catalytic domains of JAK 1 and 2 have a cysteine-based redox switch. Thus, we postulated that the NO sibling and thiophylic compound, nitroxyl (HNO), would inhibit LIF-induced JAK-STAT3 activation. Pretreatment of human microvascular endothelial cells (HMEC-1) or neonatal rat cardiomyocytes with the HNO donors Angeli's salt or nitrosocyclohexyl acetate (NCA) inhibited LIF-induced STAT3 activation. NCA pretreatment also blocked the induction of downstream inflammatory genes (e.g. intercellular adhesion molecule 1, CCAAT/enhancer binding protein delta). The related 1-nitrosocyclohexyl pivalate (NCP;not a nitroxyl donor) was equally effective in inhibiting STAT3 activation, suggesting that these compounds act as thiolate targeting electrophiles. The JAK1 redox switch is likely not a target of acyloxy nitroso compounds, as NCA had no effect on JAK1 catalytic activity and only modestly affected JAK1-induced phosphorylation of the LIF receptor. However, pretreatment of recombinant human STAT3 with NCA or NCP reduced labeling of free sulfhydryl residues. We show that NCP in the presence of diamide enhanced STAT3 glutathionylation and dimerization in adult mouse cardiac myocytes and altered STAT3 under non-reducing conditions. Finally, we show that monomeric STAT3 levels are decreased in the Gaq model of heart failure in a redox-sensitive manner. Altogether, our evidence indicates that STAT3 has redox- sensitive cysteines that regulate its activation and are targeted by HNO donors and acyloxy nitroso compounds. These findings raise the possibility of new therapeutic strategies to target STAT3 signaling via a redox-dependent manner, particularly in the context of cardiac and non-cardiac diseases with prominent pro-inflammatory signaling. [ABSTRACT FROM AUTHOR]

This study assesses the level of job and career satisfaction, work, social life and child care conflict of full time female academic physicians, and compares it with full time female non medical academicians at the American University of Beirut. The authors show that female physicians were significantly more satisfied with resources and income than non physicians. Both groups were satisfied with their job in general, yet less of the non medical academicians were satisfied with the career progress. Furthermore, despite the fact that both categories, if given the choice, would go again for the same major and the same career, yet less of the physicians would advise a friend to follow the same career. There is minimal conflict between social life and work; and being married and having children did not affect the satisfaction level except for the fact of feeling more torn between the demands of work and personal life. Several interpretations are exposed in order to explain the findings, as well as the implications of the study. [ABSTRACT FROM AUTHOR]

DNA replication stress has the potential to compromise genomic stability and, therefore, cells have developed elaborate mechanisms to detect and resolve problems that may arise during DNA replication. The presence of single-stranded DNA (ssDNA) is often associated with DNA replication stress and serves as a signal for both checkpoint and repair responses. In this study, we exploited a CRISPR-Cas9 system to induce regions of ssDNA in the genome. Specifically, single-guide RNAs bearing sequence complementarity to human telomeric repeats, were used to target nuclease-deficient Cas9 (dCas9) to telomeres. Such targeting was associated with the formation of DNA-RNA hybrids, leaving one telomeric DNA strand single-stranded. This ssDNA then recruited DNA repair and checkpoint proteins, such as RPA, ATRIP, BLM and Rad51, at the telomeres. Interestingly, targeting of all these proteins to telomeric ssDNA was observed even in cells that were in the G1 phase of the cell cycle. Therefore, this system has the potential to serve as a platform for further investigation of DNA replication stress responses at specific loci in the human genome and in all phases of the cell cycle. [ABSTRACT FROM AUTHOR]

Summary: We studied the association between CYP2R1 genetic polymorphisms and circulating 25-hydroxyvitamin D [25(OH)D] before and after supplementation with vitamin D3 in 218 elderly. We found differences between 3 and 8 ng/ml in circulating levels at baseline in women but not in the response after 1 year of supplementation. Introduction: This study evaluated the association between polymorphisms in four single nucleotide polymorphisms (SNPs) of the CYP2R1 gene and 25(OH)D levels before and 1 year after supplementation with two different doses of vitamin D3 (600 IU daily or a dose equivalent to 3750 IU daily), in a cohort of 218 (96 men and 122 women) Lebanese elderly overweight subjects. Methods: Genotyping was performed for rs12794714, rs10741657, rs1562902, and rs10766197 SNPs using real-time PCR. The 25(OH)D levels were measured by liquid chromatography tandem mass spectrometry. Results: At baseline, the mean ± SD age was 71.0 ± 4.7 years, BMI 30.3 ± 4.6 kg/m, and 25(OH)D level was 20.5 ± 7.6 ng/ml. There were significant differences in mean 25(OH)D levels between genotypes in women, but not in men. After adjustment for age, season, and BMI, the homozygous for the low frequency gene variant (HLV) of rs1562902 and rs10741657 SNPs had the highest mean 25(OH)D levels with difference of 7.6 ng/ml for rs1562902 SNP ( p < 0.01) and of 5.9 ng/ml for rs10741657 ( p = 0.05) compared to the homozygous for the major polymorphisms (HMPs). Conversely, for rs10766197 and rs12794714 SNPs, HMP had the highest mean 25(OH)D levels with difference of 6 ng/ml for rs10766197 ( p = 0.003) and of 4.8 ng/ml ( p = 0.02) for rs12794714, compared to the HLV. CYP2R1 genetic polymorphisms explained 4.8 to 9.8 % of variability in 25(OH)D in women. After 1 year, there was no difference in the response to vitamin D3 supplementation between genotypes in either gender. Conclusion: This study showed a difference in 25(OH)D levels between CYP2R1 genotypes that equates a daily supplementation of 400-800 IU vitamin D, depending on genotype. It underscores possible important genetic contributions for the high prevalence of hypovitaminosis D in the Middle East. [ABSTRACT FROM AUTHOR]

Despite the central role of the liver in drug metabolism, surprisingly there is lack of certainty in anticipating the extent of modification of the clearance of a given drug in a given patient. The intent of this review is to provide a conceptual framework in considering the impact of liver disease on drug disposition and reciprocally the impact of drug disposition on liver disease. It is proposed that improved understanding of the situation is gained by considering the issue as a special example of a drug–gene–environment interaction. This requires an integration of knowledge of the drug’s properties, knowledge of the gene products involved in its metabolism, and knowledge of the pathophysiology of its disposition. This will enhance the level of predictability of drug disposition and toxicity for a drug of interest in an individual patient. It is our contention that advances in pharmacology, pharmacogenomics, and hepatology, together with concerted interests in the academic, regulatory, and pharmaceutical industry communities provide an ideal immediate environment to move from a qualitative reactive approach to quantitative proactive approach in individualizing patient therapy in liver disease. [ABSTRACT FROM PUBLISHER]

Background:The Faculty of Medicine at the American University of Beirut implemented a new medical curriculum, which included 90 team-based learning (TBL) sessions in years 1 and 2 of medical school. Methods:A validated team performance scale (TPS) and peer evaluation of communication skills, professionalism and personal development were collected at different time points during the two years. Grades on the individual and group readiness assurance tests and an evaluation form were collected after every TBL session. Results:Students generally positively evaluated most TBL sessions as promoters of critical thinking and appreciated the self-learning experience, though they preferred and had better individual grades on those that entailed preparation of didactic lectures. There was a sustained and cumulative improvement in teamwork skills over time. Similar improvement was noted with peer evaluations of communication skills, professionalism, and personal development over time. Conclusions:This is the first report about such a longitudinal follow-up of medical students who were exposed to a large number of TBL sessions over two years. The results support the suggestion that TBL improves medical students’ team dynamics and their perceived self-learning, problem solving and communication skills, as well as their professionalism and personal development. [ABSTRACT FROM PUBLISHER]

Background Microscopic and clinical classifications of cutaneous leishmania have been set in the 1980s. Since then, they have been used invariably. Lebanon, a nonendemic country, is suffering from a leishmaniasis epidemic because of the massive population influx from endemic Syria. Design Patients diagnosed and speciated with leishmania (n = 169) using molecular and microscopic analysis were studied. General demographic data, microscopic data [Ridley's pattern ( RP), microscopic pattern, Parasitic Index ( PI)] and clinical stage were documented. Clinical score was scored as: 1: inflammatory; 2: proliferative/reorganization; 3: healed phases. The three patterns were studied in comparison to the lesion age and PI. Results At low PI, the clinical score and microscopic pattern showed healing scores (scores 3 and 4, respectively). In contrast, RP showed variable distribution at low PI. The same pattern is noted when correlating the different patterns with high PI. In comparison to lesion age, none of the three patterns showed the predicted linear correlation with lesion progression. Conclusion In the studied population, the previously adopted classifications did not correlate with the disease progression. Such findings may raise the possibility of evolving disease. The proposed clinical and microscopic patterns showed better correlation with the disease progression. [ABSTRACT FROM AUTHOR]

We observe a sample of n independent p -dimensional Gaussian vectors with Toeplitz covariance matrix Σ = [ σ ∣ i − j ∣ ] 1 ≤ i , j ≤ p and σ 0 = 1 . We consider the problem of testing the hypothesis that Σ is the identity matrix asymptotically when n → ∞ and p → ∞ . We suppose that the covariances σ k decrease either polynomially ( ∑ k ≥ 1 k 2 α σ k 2 ≤ L for α > 1 / 4 and L > 0 ) or exponentially ( ∑ k ≥ 1 e 2 A k σ k 2 ≤ L for A , L > 0 ). We consider a test procedure based on a weighted U-statistic of order 2, with optimal weights chosen as solution of an extremal problem. We give the asymptotic normality of the test statistic under the null hypothesis for fixed n and p → + ∞ and the asymptotic behavior of the type I error probability of our test procedure. We also show that the maximal type II error probability, either tend to 0 , or is bounded from above. In the latter case, the upper bound is given using the asymptotic normality of our test statistic under alternatives close to the separation boundary. Our assumptions imply mild conditions: n = o ( p 2 α − 1 / 2 ) (in the polynomial case), n = o ( e p ) (in the exponential case). We prove both rate optimality and sharp optimality of our results, for α > 1 in the polynomial case and for any A > 0 in the exponential case. A simulation study illustrates the good behavior of our procedure, in particular for small n , large p . [ABSTRACT FROM AUTHOR]

Background: Ovarian 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. Methods: We 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. Results: Cytotoxicity 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. Conclusion: Our 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. [ABSTRACT FROM AUTHOR]

Diabetic skin has impaired wound healing properties following injury. We have further shown that diabetic skin has weakened biomechanical properties at baseline. We hypothesize that the biomechanical properties of diabetic skin decline during the progression of the diabetic phenotype, and that this decline is due to the dysregulation of miR-29a, resulting in decreased collagen content. We further hypothesize that treatment with mesenchymal stem cells (MSCs) may improve diabetic wound healing by correction of the dysregulated miR-29a expression. We analyzed the biomechanical properties, collagen gene expression, collagen protein production, and miR-29a levels in skin harvested from 6 to 18 week old mice during the development of the diabetic phenotype. We also examined the correction of these impairments by both MSC treatment and the inhibition of miR-29a. Diabetic skin demonstrated a progressive impairment of biomechanical properties, decreased collagen content, and increased miR-29a levels during the development of the diabetic phenotype. MSC treatment decreased miR-29a levels, increased collagen content, and corrected the impaired biomechanical properties of diabetic skin. Additionally, direct inhibition of miR-29a also increased collagen content in diabetic skin. This decline in the biomechanical properties of diabetic skin during the progression of diabetes may increase the susceptibility of diabetic skin to injury and miR-29a appears to play a key role in this process. [ABSTRACT FROM AUTHOR]