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Dissection of bodies provided by donors continues to be utilized as a critical part of medical education. It also represents a rite of passage that socializes students to prepare them for the stress that comes with working in a clinical environment as a medical professional. Just as proper guidance in acquiring technical skills is critical in anatomy education, there is an important need for proper emotional guidance throughout the human dissection process. A pilot curriculum was developed by an interdisciplinary faculty team to emotionally prepare students for their first visit to the anatomy laboratory. Students were first-year foundation premedical students who had expressed an interest in visiting the laboratory. Pre- and post-visit surveys were conducted to explore students' emotional responses to a first visit to the anatomy laboratory and their utilization of coping strategies. The survey findings show an overwhelming favorable feeling in anticipation of the human gross anatomy laboratory visit. About 20% of the students experienced anxiety at the anticipation of the laboratory visit, but only 5.3% experienced anxiety during the visit. The decrease in the number of students experiencing anxiety may be attributed to the interventions introduced before and during the visit. Talking with a close friend was the main coping strategy utilized by 63% of students experiencing fear or anxiety during and after the laboratory visit. The findings from this program evaluation provide a better understanding of student emotional preparedness and utilization of coping strategies, which may help prepare and guide future students for the dissection experience.

The need for reliable biomarkers to predict clinical benefit from anti-PD1 treatment in metastatic melanoma (MM) patients remains unmet. Several parameters have been considered in the tumor environment or the blood, but none has yet achieved sufficient accuracy for routine clinical practice. Whole blood samples from MM patients receiving second-line anti-PD1 treatment (NCT02626065), collected longitudinally, were analyzed by flow cytometry to assess the immune cell subsets absolute numbers, the expression of immune checkpoints or ligands on T cells and the functionality of innate immune cells and T cells. Clinical response was assessed according to Progression-Free Survival (PFS) status at one-year following initiation of anti-PD1 (responders: PFS > 1 year; non-responders: PFS ≤ 1 year). At baseline, several phenotypic and functional alterations in blood immune cells were observed in MM patients compared to healthy donors, but only the proportion of polyfunctional memory CD4+ T cells was associated with response to anti-PD1. Under treatment, a decreased frequency of HVEM on CD4+ and CD8+ T cells after 3 months of treatment identified responding patients, whereas its receptor BTLA was not modulated. Both reduced proportion of CD69-expressing CD4+ and CD8+ T cells and increased number of polyfunctional blood memory T cells after 3 months of treatment were associated with response to anti-PD1. Of upmost importance, the combination of changes of all these markers accurately discriminated between responding and non-responding patients. These results suggest that drugs targeting HVEM/BTLA pathway may be of interest to improve anti-PD1 efficacy.

Abstract The metric on the hypermultiplet moduli space of Calabi-Yau compactifications of type II string theory is known to receive D-brane and NS5-brane instanton corrections. We compute explicit expressions for these corrections in the one-instanton approximation, but to all orders in the string coupling expansion around the instantons. As a consistency check, we prove that in the case of one (universal) hypermultiplet, the resulting metric fits the Przanowski description of self-dual Einstein spaces. We also show that in the small string coupling limit the metric acquires a certain square structure, consistently with expectations from the string amplitudes analysis. This result provides explicit predictions for yet mysterious string amplitudes in the presence of NS5-branes.

Apple crops are prone to several diseases that limit their production—in particular, root rot caused by a new genus of oomycetes, mainly Phytopythium vexans. This study aims to screen antagonistic bacteria that can play an important role in the biological control of this pathogenic oomycete and to evaluate their capacity to promote plant growth. The dual culture test revealed that, out of 200 bacterial isolates, 16 have been able to inhibit the mycelial growth of P. vexans with inhibition rates greater than 50%. The selected isolates were identified based on the 16S rDNA genes: 14 bacteria belonging to the genus Bacillus, Stenotrophomonas, and the family Enterobacteriaceae. Notably, two isolates, B1 and M2-6 (identified as Bacillus velezensis), demonstrated the highest inhibition rates of 70% and 68%, respectively. These selected isolates were examined for their ability to produce different compounds related to biocontrol and plant growth promotion. Furthermore, the 16 selected isolates were evaluated for their ability to produce compounds associated with biocontrol and plant growth promotion, including hydrolytic enzymes (cellulases, proteases, and amylases), HCN (hydrogen cyanide) production, phosphate solubilization, IAA (indole-3-acetic acid) production, pectinase production, and stimulation of sorghum bicolor growth in vivo. Variations were observed among the bacterial isolates in terms of their compound production and phytostimulation capabilities. However, the secretion of proteases was consistently detected in all antagonistic isolates. The presence of genes responsible for the production of antifungal lipopeptides (bacillomycin, fengycin, and iturin) in the selected bacterial isolates was determined using polymerase chain reaction (PCR) techniques, while the absence of genes involved in surfactin biosynthesis was also confirmed through PCR studies. These isolates demonstrated inhibitory activity through the production of proteases and antifungal lipopeptides. Further research is needed to explore their potential use in biological control strategies and to improve apple crop productivity.

Akash Keluth Chavan,1 Rachid Bendriss2 1Medical Education, Weill Cornell Medicine-Qatar, Doha, Qatar; 2Premedical Education, Weill Cornell Medicine-Qatar, Doha, QatarCorrespondence: Rachid Bendriss, Premedical Education Division, Weill Cornell Medicine-Qatar, P.O. Box 24144, Doha, Qatar, Tel +974 4492 8221, Email rab2029@qatar-med.cornell.eduPurpose: Leadership has long been recognized as a core competency required to excel in medical practice. This qualitative study investigates the extent to which leadership competencies are incorporated in the curriculum of a US medical college in Qatar and examines the perceptions of medical students and faculty about leadership in the medical curriculum.Methods: The study uses a student survey, faculty interviews, and a student focus group to gather data.Results: The study found that 79% of the survey respondents perceive leadership as a core competency while 55% feel that leadership skills are not adequately taught to students. The focus group and interviews revealed that students believe more importance should be given to leadership training whereas faculty assert that, while leadership can be beneficial, leadership training is implicit, and more research is required for further implementation.Conclusion: This study shows the need for an increased emphasis on developing leadership curricula in undergraduate medical education and highlights ways to address certain obstacles to implementation. Further research on exploring medical alumni’s perceptions and optimal teaching methods to implement leadership training is needed.Keywords: leadership in medical curriculum, leadership training, future doctors, Qatar, medical education

This study describes the implementation of information literacy (IL) skills through the use of the project-based learning (PjBL) method in an English for Academic Purposes (EAP) course. Participants were Arabic speaking students enrolled in the Foundation Program that prepared them for the pre-medical curriculum in a U.S. medical college in the State of Qatar. A mixed methods approach consisting of a survey, three focus groups, and instructors' observations was used to gather the needed data. The results showed a significant increase in students' advanced research skills. This study emphasizes the benefit of using the PjBL method to develop students' IL skills. It also reinforces the vital role of faculty-librarian partnership in designing learning activities that engage students, foster their critical thinking, and develop their metacognitive skills.

Obesity and psychiatric disorders are linked through a bidirectional association. Obesity rates have tripled globally in the past decades, and it is predicted that by 2025, one billion people will be affected by obesity, often with a co-morbidity such as depression. While this co-morbidity seems to be a global health issue, lifestyle factors associated to it differ between countries and are often attributed to more than one factor. Prior obesity studies were performed in Western populations; this is the first study that investigates lifestyle factors relating to obesity and mental health of the diverse population in Qatar, a country that has witnessed tremendous lifestyle change in a short time. In this pilot study, we surveyed 379 respondents to assess and compare the lifestyles of Qatar residents to the global population. However due to the high proportion of responses from the United Kingdom (UK) residents, we have made comparisons between Qatar residents and UK residents. We used chi-square analysis, spearman rank correlation and logistic regression to compare the lifestyle factors of individuals suffering from both increased BMI and mental health conditions. The types of food consumed, stress, exercise frequency and duration, alcohol and tobacco consumption, and sleep duration, were explored and results argue that different lifestyle factors can contribute to the same health condition, suggesting different mechanisms involved. We found that both groups reported similar sleep durations (p = 0.800), but that perception of sleep (p = 0.011), consumption of alcohol (p = 0.001), consumption of takeaway food (p = 0.007), and physical activity significantly varied between the groups (p = 0.0001). The study examined the predictors of comorbidity in Qatar as well as UK populations using multivariate logistic regression analysis. The result of the study showed no statistical association between comorbidity and the predictors drinking habit, smoking, physical activity, vegetable consumption, eat outs, and sleep perception for the Qatar population, and for the combined population. This study, however showed a significant association (p = 0.033) between sleep perception and comorbidity for the UK population. We conclude that further analysis is needed to understand the relationship between specific lifestyle factors and multimorbidity in each country.

Dissection of bodies provided by donors continues to be utilized as a critical part of medical education. It also represents a rite of passage that socializes students to prepare them for the stress that comes with working in a clinical environment as a medical professional. Just as proper guidance in acquiring technical skills is critical in anatomy education, there is an important need for proper emotional guidance throughout the human dissection process. A pilot curriculum was developed by an interdisciplinary faculty team to emotionally prepare students for their first visit to the anatomy laboratory. Students were first‐year foundation premedical students who had expressed an interest in visiting the laboratory. Pre‐ and post‐visit surveys were conducted to explore students' emotional responses to a first visit to the anatomy laboratory and their utilization of coping strategies. The survey findings show an overwhelming favorable feeling in anticipation of the human gross anatomy laboratory visit. About 20% of the students experienced anxiety at the anticipation of the laboratory visit, but only 5.3% experienced anxiety during the visit. The decrease in the number of students experiencing anxiety may be attributed to the interventions introduced before and during the visit. Talking with a close friend was the main coping strategy utilized by 63% of students experiencing fear or anxiety during and after the laboratory visit. The findings from this program evaluation provide a better understanding of student emotional preparedness and utilization of coping strategies, which may help prepare and guide future students for the dissection experience. [ABSTRACT FROM AUTHOR]

Subversion of immunity by tumors is a crucial step for their development. Dendritic cells (DCs) are strategic immune cells that orchestrate anti-tumor immune responses but display altered functions in cancer. The bases for such DCs’ hijacking are not fully understood. Tumor cells harbor unusual glycosylation patterns of surface glycoproteins and glycolipids. DCs express glycan-binding receptors, named C-type lectin receptors (CLR), allowing them to sense changes in glycan signature of their environment, and subsequently trigger a response. Recognition of tumor glycans by CLRs is crucial for DCs to shape antitumor immunity, and decisive in the orientation of the response. Yet the status of the CLR machinery on DCs in cancer, especially melanoma, remained largely unknown. We explored CLR expression patterns on circulating and tumor-infiltrating cDC1s, cDC2s, and pDCs of melanoma patients, assessed their clinical relevance, and further depicted the correlations between CLR expression profiles and DCs’ features. For the first time, we highlighted that the CLR repertoire of circulating and tumor-infiltrating cDC1s, cDC2s, and pDCs was strongly perturbed in melanoma patients, with modulation of DCIR, CLEC-12α and NKp44 on circulating DCs, and perturbation of Dectin-1, CD206, DEC205, DC-SIGN and CLEC-9α on tumor-infiltrating DCs. Furthermore, melanoma tumor cells directly altered CLR expression profiles of healthy DC subsets, and this was associated with specific glycan patterns (Man, Fuc, GlcNAc) that may interact with DCs through CLR molecules. Notably, specific CLR expression profiles on DC subsets correlated with unique DCs’ activation status and functionality and were associated with clinical outcome of melanoma patients. Higher proportions of DCIR-, DEC205-, CLEC-12α-expressing cDCs were linked with a better survival, whereas elevated proportions of CD206-, Dectin1-expressing cDCs and NKp44-expressing pDCs were associated with a poor outcome. Thus, melanoma tumor may shape DCs’ features by exploiting the plasticity of the CLR machinery. Our study revealed that melanoma manipulates CLR pathways to hijack DC subsets and escape from immune control. It further paved the way to exploit glycan-lectin interactions for the design of innovative therapeutic strategies, which exploit DCs’ potentialities while avoiding hijacking by tumor, to properly reshape anti-tumor immunity by manipulating the CLR machinery.

Obsessive–compulsive disorder (OCD) is a debilitating mental health disorder characterized by intrusive thoughts (obsessions) and repetitive behaviors (compulsions). Dysbiosis, an imbalance in the gut microbial composition, has been associated with various health conditions, including mental health disorders, autism, and inflammatory diseases. While the exact mechanisms underlying OCD remain unclear, this review presents a growing body of evidence suggesting a potential link between dysbiosis and the multifaceted etiology of OCD, interacting with genetic, neurobiological, immunological, and environmental factors. This review highlights the emerging evidence implicating the gut microbiota in the pathophysiology of OCD and its potential as a target for novel therapeutic approaches. We propose a model that positions dysbiosis as the central unifying element in the neurochemical, immunological, genetic, and environmental factors leading to OCD. The potential and challenges of microbial reprogramming strategies, such as probiotics and fecal transplants in OCD therapeutics, are discussed. This review raises awareness of the importance of adopting a holistic approach that considers the interplay between the gut and the brain to develop interventions that account for the multifaceted nature of OCD and contribute to the advancement of more personalized approaches.

Background The efficacy of immunotherapies in metastatic melanoma depends on a robust T cell infiltration. Oncogenic alterations of tumor cells have been associated to T cell exclusion. Identifying novel cancer cell-intrinsic non-genetic mechanisms of immune escape, the targeting of which would reinstate T cell recruitment, would allow to restore the response to anti-programmed cell death protein 1 (PD-1) antibody therapy. The epithelial-to-mesenchymal transition (EMT)-inducing transcription factor ZEB1 is a major regulator of melanoma cell plasticity, driving resistance to mitogen-activated protein kinase (MAPK) targeted therapies. We thus wondered whether ZEB1 signaling in melanoma cells may promote immune evasion and resistance to immunotherapy.Methods We evaluated the putative correlation between ZEB1 expression in melanoma cells and the composition of the immune infiltrate in a cohort of 60 human melanoma samples by combining transcriptomic (RNA-sequencing) and seven-color spatial multi-immunofluorescence analyses. Algorithm-based spatial reconstitution of tumors allowed the quantification of CD8+, CD4+ T cells number and their activation state (PD-1, Ki67). ZEB1 gain-of-function or loss-of-function approaches were then implemented in syngeneic melanoma mouse models, followed by monitoring of tumor growth, quantification of immune cell populations frequency and function by flow cytometry, cytokines secretion by multiplex analyses. Chromatin-immunoprecipitation was used to demonstrate the direct binding of this transcription factor on the promoters of cytokine-encoding genes. Finally, the sensitivity to anti-PD-1 antibody therapy upon ZEB1 gain-of-function or loss-of-function was evaluated.Results Combined spatial and transcriptomic analyses of the immune infiltrates in human melanoma samples demonstrated that ZEB1 expression in melanoma cells is associated with decreased CD8+ T cell infiltration, independently of β-catenin pathway activation. ZEB1 ectopic expression in melanoma cells impairs CD8+ T cell recruitment in syngeneic mouse models, resulting in tumor immune evasion and resistance to immune checkpoint blockade. Mechanistically, we demonstrate that ZEB1 directly represses the secretion of T cell-attracting chemokines, including CXCL10. Finally, Zeb1 knock-out, by promoting CD8+ T cell infiltration, synergizes with anti-PD-1 antibody therapy in promoting tumor regression.Conclusions We identify the ZEB1 transcription factor as a key determinant of melanoma immune escape, highlighting a previously unknown therapeutic target to increase efficacy of immunotherapy in melanoma.Trial registration number NCT02828202.

Anti-Ly6G or ant-Gr1 antibodies are commonly used to deplete neutrophils in vivo. Here the authors provide mechanistic insight into why these approaches may not specifically or durably reduce the number of neutrophils in mice, and also present a new method that overcomes these limitations to have potentially wide applicability in experimental studies.

Atlas cedar (Cedrus atlantica (Endl.) G. Manetti ex Carrière) is an endemic species in the mountains of North Africa that is attracting international interest in its use in the reforestation of degraded ecosystems. This study aims to investigate and evaluate the morphoanatomical characteristics of needles of four cedar populations localized in the Middle and High Atlas Mountains. Descriptive statistics, analysis of variance (ANOVA), descriptive power, scatter-plot of the discrimination function, scatter-plot of discrimination, and dendrogram of the closest Euclidean distances were made on traits. The results of the linear model of ANOVA nested as population and tree within population suggest the differences statistically significant for the traits measured at a different level. Among these traits, the length of the needle, the width of a vascular bundle including endodermis, and thickness of the wall of hypodermis cell revealed the highest discriminating characters among populations of C. atlantica from the Middle and High Atlas and between the populations of the Middle Atlas. The agglomeration of populations over short Euclidean distances also showed a higher level of differentiation between two ecotypes of C. atlantica not very geographically distant in the Atlas Mountains of Morocco. The ecotype belonging to Aït Oufella and Aït Ayach confers this species a place of choice in the projects of revalorization of the Mediterranean populations, especially in semiarid areas.

The study of morphological and anatomical characteristics of leaves is important for assessing the geographical variation of species. The ecological adaptability of forty individuals from four populations of Cedrus atlantica were studied, based on analysis of morphological and anatomical traits. The results of the Spearman nonparametric coefficient of correlation showed that the number of stomatal lines (NLS) and the length of the needle (NL) are negatively correlated to altitude and positively to latitude and precipitation sums, while the width of the needle (NW), the thickness of the cuticle (CT), and the number of needles per rosette (NN/R) were negatively related to temperature. In addition, the sum of precipitation is negatively correlated with NW. The first two principal components account for 58.18% of the variation. According to Tukey’s test and Kruskal–Wallis test, all populations had at least three characters separating them at a statistically significant variation. Moreover, the hierarchical classification led us to the individualization of three main groups. All these results show an adaptation of the structure of the needles of C. atlantica from Morocco to the geographical position and the climatic conditions of the populations.

Abstract Objectives Plasmacytoid DCs (pDCs) play a critical yet enigmatic role in antitumor immunity through their pleiotropic immunomodulatory functions. Despite proof of pDC diversity in several physiological or pathological contexts, pDCs have been studied as a whole population so far in cancer. The assessment of individual pDC subsets is needed to fully grasp their involvement in cancer immunity, especially in melanoma where pDC subsets are largely unknown and remain to be uncovered. Methods We explored for the first time the features of diverse circulating and tumor‐infiltrating pDC subsets in melanoma patients using multi‐parametric flow cytometry, and assessed their clinical relevance. Based on CD80, PDL1, CD2, LAG3 and Axl markers, we provided an integrated overview of the frequency, basal activation status and functional features of pDC subsets in melanoma patients together with their relationship to clinical outcome. Results Strikingly, we demonstrated that P3‐pDCs (CD80+PDL1−) accumulated within the tumor of melanoma patients and negatively correlated with clinical outcomes. The basal activation status, diversification towards P1‐/P2‐/P3‐pDCs and functionality of several pDC subsets upon TLR7/TLR9 triggering were perturbed in melanoma patients, and were differentially linked to clinical outcome. Conclusion Our study shed light for the first time on the phenotypic and functional heterogeneity of pDCs in the blood and tumor of melanoma patients and their potential involvement in shaping clinical outcomes. Such novelty brightens our understanding of pDC complexity, and prompts the further deciphering of pDCs’ features to better apprehend and exploit these potent immune players. It highlights the importance of considering pDC diversity when developing pDC‐based therapeutic strategies to ensure optimal clinical success.

The cognitive sciences have witnessed a growing interest in cognitive and neural basis of human creativity. Music improvisations constitute an ideal paradigm to study creativity, but the underlying cognitive processes remain poorly understood. In addition, studies on music improvisations using scales other than the major and minor chords are scarce. Middle Eastern Music is characterized by the additional use of microtones, resulting in a tonal–spatial system called Maqam. No EEG correlates have been proposed yet for the eight most commonly used maqams. The Ney, an end-blown flute that is popular and widely used in the Middle East was used by a professional musician to perform 24 improvisations at low, medium, and high tempos. Using the EMOTIV EPOC+, a 14-channel wireless EEG headset, brainwaves were recorded and quantified before and during improvisations. Pairwise comparisons were calculated using IBM-SPSS and a principal component analysis was used to evaluate the variability between the maqams. A significant increase of low frequency bands theta power and alpha power were observed at the frontal left and temporal left area as well as a significant increase in higher frequency bands beta-high bands and gamma at the right temporal and left parietal area. This study reveals the first EEG observations of the eight most commonly used maqam and is proposing EEG signatures for various maqams.

With the WHO announcing that the Corona virus is a global pandemic, many countries have taken measures to prevent its spread, among which suspension of international transport operations; which made it difficult to implement contractual obligations. Consequently, the Corona virus pandemic brought up the issue of changing circumstances surrounding the international contract, which raised legal discussions in adapting it, is it considered a force majeure with which it is impossible to implement the contract, or is it an emergency circumstance that leads to difficult implementation in a way that disrupts the economic balance of the contract? The fact that international trade contracts are characterized by several peculiarities, appear in the efforts made to conclude them, and their extension for long periods, which made it difficult to terminate contracts due to the changing circumstances surrounding them. This is because contract parties are free to include in their contracts various conditions that give solutions to the changing circumstances. This study aims to search for the legal issues that the Corona virus epidemic raises on the international trade contract, within the frameworks of comparative legal systems and the provisions of international agreements.

Among patients with chronic kidney disease (CKD), hypertension (HTN) is very common and widely recognized to accelerate the progression of CKD and increase the risk for cardiovascular events. Accumulated data indicate that ambulatory blood pressure monitoring (ABPM) is better in detecting HTN than office blood pressure (BP) measurement. The goal of this study is to describe the ABPM characteristics in a group of CKD and hypertensive patients. A transversal study was conducted over a period of six months, to evaluate the ABPM patterns among a group of hypertensive patients with CKD (Group 1) and compared the data with a control group (Group 2). ABPM was performed with measurement rate every 15 min during daytime and 30 min at night. Nondipping BP patterns were defined as the absence of fall in nocturnal systolic and diastolic BP >10% of daytime values. Masked HTN was defined as controlled office BP (125/75 mm Hg), and white-coat HTN was defined as association of elevated BP readings (>140/90 mm Hg) in a clinical setting and normal 24-h average BP levels (

The effect of textural and physicochemical characteristics of five cedar forest soils on 4- and 8-month-old seedlings of Cedrus atlantica Manetti was studied in a controlled growth chamber. During their growth, cedar seedlings show a change in the root architecture by the levels of Corg, N, P, and by the soil granulometry. The Tioumlilin soil conditions stimulate mainly the cumulative length and the number of secondary roots. However, the cedar forest soil of Tazekka predominates over most soils in its effect on growth by the balance of chemical elements and the high percentage of coarse particles. The analysis of the densities of secondary and tertiary roots and the cumulative length of secondary roots show four different root architectural development strategies of C. atlantica seedlings which may justify the low level of mycorrhization on young seedlings in the natural cedar forest soil. The variations of the root architectural parameters of C. atlantica seedlings are discussed in relation to the characteristics of cedar forest soils.