Curriculum Setting and Pre-Clinical Dental Students' Stress Level

Objectives: The first two years of Dental School are commonly known to be the most stressful in a student’s academic career. Very few studies, however, consider both the pressures of dental school and their causes. In order to understand the relationship between the curriculum and its stressful effects it has on the first (D1) and second-year (D2) dental students, a cross-sectional study was performed at the University of New England College of Dental Medicine (UNE-CDM) during the fall and spring semesters of the 2015-2016 academic year. Methods: 64 D1 and 63 D2 dental students were asked to voluntarily complete an anonymous 27-question survey regarding demographic characteristics and the curriculum-related stressors. Researchers utilized the modified Dental Environment Scale (DES) to rate the stress levels. Results: This study revealed that the D2 students felt more stress than the D1 students overall. D2 students experienced more anxiety in their Spring semester of their second year. In general, students who lived with their immediate family felt less stress. Students twenty-five and over experienced less stress than their younger classmates. Conclusions: The study provided valuable information about the current structure of the curriculum at a newly established dental school. This study could provide insight into curriculum-related stress among pre-clinical dental students, which could guide dental schools in making curricular changes that help alleviate stressors during particularly stressful semesters. Furthermore, the outcomes of this project could provide dental schools the information necessary to develop student support programs to help balance students’ lives and intense course loads

MixInYeast: A Multicenter Study on Mixed Yeast Infections

Invasive candidiasis remains one of the most prevalent systemic mycoses, and several studies have documented the presence of mixed yeast (MY) infections. Here, we describe the epidemiology, clinical, and microbiological characteristics of MY infections causing invasive candidiasis in a multicenter prospective study. Thirty-four centers from 14 countries participated. Samples were collected in each center between April to September 2018, and they were sent to a reference center to confirm identification by sequencing methods and to perform antifungal susceptibility testing, according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST). A total of 6895 yeast cultures were identified and MY occurred in 150 cases (2.2%). Europe accounted for the highest number of centers, with an overall MY rate of 4.2% (118 out of 2840 yeast cultures). Of 122 MY cases, the most frequent combinations were Candida albicans/C. glabrata (42, 34.4%), C. albicans/C. parapsilosis (17, 14%), and C. glabrata/C. tropicalis (8, 6.5%). All Candida isolates were susceptible to amphotericin B, 6.4% were fluconazole-resistant, and two isolates (1.6%) were echinocandin-resistant. Accurate identification of the species involved in MY infections is essential to guide treatment decisions

Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity

The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management. © 2021, The Author(s)

Heterogeneous integration of terahertz electronics

Abstract: Compact heterodyne receivers operating in the terahertz range are needed for earth observation instruments, space science missions (e.g. ESA’s “Jupiter icy moons explorer - JUICE”) and in the millimeter wave region for ground-based applications such as security scanners. Existing terahertz heterodyne receivers are usually bulky due to complex hybrid integration and there is a strong need for a terahertz monolithic integration circuit (“TMIC”) platform that allows for higher circuit functionality, ease of assembly, and low loss at terahertz frequencies. Moreover, this part of the electromagnetic spectrum, where optical and microwave techniques meet, call for an integration scheme that can support both active THz electronics & photonics. A possible solution is heterogeneous integration of THz devices (III-V, graphene) on a silicon carrier, which also allows for advanced micromaching of passive components and interconnects such as waveguides and antennas. This talk provides an overview of research on integrated diode circuits for terahertz applications. Progress on heterogeneous integration of HBV multipliers and Schottky diode mixers on silicon substrates (SOI) will be presented

Heterogeneous integration of terahertz electronics

Abstract: Compact heterodyne receivers operating in the terahertz range are needed for earth observation instruments, space science missions (e.g. ESA’s “Jupiter icy moons explorer - JUICE”) and in the millimeter wave region for ground-based applications such as security scanners. Existing terahertz heterodyne receivers are usually bulky due to complex hybrid integration and there is a strong need for a terahertz monolithic integration circuit (“TMIC”) platform that allows for higher circuit functionality, ease of assembly, and low loss at terahertz frequencies. Moreover, this part of the electromagnetic spectrum, where optical and microwave techniques meet, call for an integration scheme that can support both active THz electronics & photonics. A possible solution is heterogeneous integration of THz devices (III-V, graphene) on a silicon carrier, which also allows for advanced micromaching of passive components and interconnects such as waveguides and antennas. This talk provides an overview of research on integrated diode circuits for terahertz applications. Progress on heterogeneous integration of HBV multipliers and Schottky diode mixers on silicon substrates (SOI) will be presented

Mdm2 and MdmX inhibitors for the treatment of cancer:a patent review (2011-present)

Introduction: One of the hallmarks of cancer cells is the inactivation of the p53 pathway either due to mutations in the p53 gene or over-expression of negative regulators, Mdm2 and/or MdmX. Pharmacological disruption of the Mdm2/X-p53 interaction to restore p53 activity is an attractive concept, aiming at a targeted and non-toxic cancer treatment. Areas covered: The introduction covers the biological role of p53 pathway and its regulation by Mdm2 and MdmX in normal and cancer cells and the current repertoire and development status of inhibitors of the Mdm2/X-p53 interaction for the treatment of cancer. The main part of the article covers patents and patent applications describing small molecule inhibitors of the Mdm2/X-p53 interaction published from 2011 until 2012. Expert opinion: The area of small molecule Mdm2/X-p53 interaction inhibitor development is progressing fast. Several Phase I clinical studies and preclinical programs are now in progress, however, the clinical proof concept has yet to be demonstrated. Multiple available compounds inhibit Mdm2-p53 interaction with nanomolar affinities, but MdmX is still missing such potent binders. Since research points to a complementary mode of Mdm2 and MdmX action, the future compound classes will possibly want to include dual actions versus Mdm2 and MdmX

The Application of Artificial Intelligence-Assisted Colposcopy in a Tertiary Care Hospital within a Cervical Pathology Diagnostic Unit

The rising global incidence of cervical cancer is estimated to have affected more than 600,000 women, and nearly 350,000 women are predicted to have died from the disease in 2020 alone. Novel advances in cancer prevention, screening, diagnosis and treatment have all but reduced the burden of cervical cancer in developed nations. Unfortunately, cervical cancer is still the number one gynecological cancer globally. A limiting factor in managing cervical cancer globally is access to healthcare systems and trained medical personnel. Any methodology or procedure that may simplify or assist cervical cancer screening is desirable. Herein, we assess the use of artificial intelligence (AI)-assisted colposcopy in a tertiary hospital cervical diagnostic pathology unit. The study group consisted of 48 women (mean age 34) who were referred to the clinic for a routine colposcopy by their gynecologist. Cervical images were taken by an EVA-Visualcheck TM colposcope and run through an AI algorithm that gave real-time binary results of the cervical images as being either normal or abnormal. The primary endpoint of the study assessed the AI algorithm’s ability to correctly identify histopathology results of CIN2+ as being abnormal. A secondary endpoint was a comparison between the AI algorithm and the clinical assessment results. Overall, we saw lower sensitivity of AI (66.7%; 12/18) compared with the clinical assessment (100%; 18/18), and histopathology results as the gold standard. The positive predictive value (PPV) was comparable between AI (42.9%; 12/28) and the clinical assessment (41.8%; 18/43). The specificity, however, was higher in the AI algorithm (46.7%; 14/30) compared to the clinical assessment (16.7%; 5/30). Comparing the congruence between the AI algorithm and histopathology results showed agreement 54.2% of the time and disagreement 45.8% of the time. A trained colposcopist was in agreement 47.9% and disagreement 52.1% of the time. Assessing these results, there is currently no added benefit of using the AI algorithm as a tool of speeding up diagnosis. However, given the steady improvements in the AI field, we believe that AI-assisted colposcopy may be of use in the future

A Unique Mdm2-Binding Mode of the 3-Pyrrolin-2-one- and 2-Furanone-Based Antagonists of the p53-Mdm2 Interaction

The p53 pathway is inactivated in almost all types of cancer by mutations in the p53 encoding gene or overexpression of the p53 negative regulators, Mdm2 and/or Mdmx. Restoration of the p53 function by inhibition of the p53-Mdm2/Mdmx interaction opens up a prospect for a nongenotoxic anticancer therapy. Here, we present the syntheses, activities, and crystal structures of two novel classes of Mdm2-p53 inhibitors that are based on the 3-pyrrolin-2-one and 2-furanone scaffolds. The structures of the complexes formed by these inhibitors and Mdm2 reveal the dimeric protein molecular organization that has not been observed in the small-molecule/Mdm2 complexes described until now. In particular, the 6-chloroindole group does not occupy the usual Trp-23 pocket of Mdm2 but instead is engaged in dimerization. This entirely unique binding mode of the compounds opens new possibilities for optimization of the Mdm2-p53 interaction inhibitors

CCDC 981829: Experimental Crystal Structure Determination

Related Article: Constantinos G. Neochoritis, Kan Wang, Natalia Estrada-Ortiz, Eberhardt Herdtweck, Katarzyna Kubica, Aleksandra Twarda, Krzysztof M. Zak, Tad A. Holak, Alexander Dömling|2015|Bioorg.Med.Chem.Lett.|25|5661|doi:10.1016/j.bmcl.2015.11.019,An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

CCDC 981828: Experimental Crystal Structure Determination

Related Article: Constantinos G. Neochoritis, Kan Wang, Natalia Estrada-Ortiz, Eberhardt Herdtweck, Katarzyna Kubica, Aleksandra Twarda, Krzysztof M. Zak, Tad A. Holak, Alexander Dömling|2015|Bioorg.Med.Chem.Lett.|25|5661|doi:10.1016/j.bmcl.2015.11.019,An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.