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Anna-Lena Klauser,1 Marc Hirschfeld,1– 3 Andrea Ritter,1,2 Gerta Rücker,1,4 Markus Jäger,1,2 Julia Gundarova,1 Daniela Weiss,1,2 Ingolf Juhasz-Böss,1,2 Kai Berner,1,2 Thalia Erbes,1,2 Jasmin Asberger1,2 1Faculty of Medicine, University of Freiburg, Freiburg, Germany; 2Department of Obstetrics and Gynecology, Medical Center – University of Freiburg, Freiburg, Germany; 3Institute of Veterinary Medicine, University of Göttingen, Göttingen, Germany; 4Institute of Medical Biometry and Statistics, Medical Center – University of Freiburg, Freiburg, GermanyCorrespondence: Jasmin AsbergerDepartment of Obstetrics and Gynecology, Faculty of Medicine and Medical Center – University of Freiburg, Hugstetterstr. 55, Freiburg, 79106, GermanyTel +49 761 270 30020Fax +49 761 270 30370Email jasmin.asberger@uniklinik-freiburg.dePurpose: In 2020, breast cancer still represents the most common type of cancer in women worldwide. Depending on the specific molecular subtype, clinical breast cancer management comprises surgery, radiotherapy, chemotherapy and targeted therapy. Furthermore, there are some therapeutic approaches from the field of complementary and alternative medicine. Current research focuses on the elucidation of new therapeutic targets for treatment development. Odorant substances affect apoptosis, proliferation and cell cycle in healthy and cancerous cells. Exact signalling pathways involved are not entirely clear. The present study aims to analyse their therapeutic potential in breast cancer.Methods: This study focuses on the effect of commonly used odorant substances (citral, citrathal R, cyclovertal, para-cymol, hexylacetat, herbavert, dihydromyrcerol and limonen) on the breast cancer cell lines MDA-MB-231, T47-D and BT474. Methodologically, this study applied cell culturing, MTT assay for detection of IC50 of the odorant substance, RNA purification followed by qRT-PCR, protein isolation and Western Blot, as well as immunocytochemistry. Further, this study investigates the role of transient receptor potential channel V1 (TRPV1), involved in the mechanisms of action for some odorant substances. Therefore, capsazepine, a TRPV1 antagonist, was used.Results: The odorant substances citral, citrathal R and cyclovertal have significant pro-apoptotic (p < 0.001), anti-proliferative (p < 0.001) and cell cycle-arresting effects measurable in RNA expression as well as in protein levels and immunocytochemical staining. The combination of citral and capsazepine no longer showed significant pro-apoptotic, antiproliferative, and cell cycle inhibitory effects compared to the compounds alone. This indicates that TRPV1 is necessary for the signal transduction of citral.Conclusion: This present study reveals three odorant substances with effects on cell viability, indicating their potential use in breast cancer therapy.Keywords: citral, citrathal R, cyclovertal, odorant substances, olfactory receptor and breast cancer

Daniel Weiss,1,2 Christine Erie,1,2 Joseph Butera III,2 Ryan Copt,2 Glenn Yeaw,2 Mark Harpster,2 James Hughes,2,3 Deeb N Salem4 1Department of Medicine, Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, FL, USA; 2Bongiovi Medical & Health Technologies, Inc., Port St Lucie, FL, USA; 3Department of Surgery, University of Mississippi Medical Center, Jackson, MS, USA; 4Department of Medicine, Tufts Medical Center, Boston, MA, USA Purpose: To compare the performance of various commercially available stethoscopes using standard acoustic engineering criteria, under recording studio conditions.Materials and methods: Eighteen stethoscopes (11 acoustic, 7 electronic) were analyzed using standard acoustic analysis techniques under professional recording studio conditions. An organic phantom that accurately simulated chest cavity acoustics was developed. Test sounds were played via a microphone embedded within it and auscultated at its surface by the stethoscopes. Recordings were made through each stethoscope’s binaurals and/or downloaded (electronic models). Recordings were analyzed using standard studio techniques and software, including assessing ambient noise (AMB) rejection. Frequency ranges were divided into those corresponding to various standard biological sounds (cardiac, respiratory, and gastrointestinal).Results: Loudness and AMB rejection: Overall, electronic stethoscopes, when set to a maximum volume, exhibited greater values of perceived loudness compared to acoustic stethoscopes. Significant variation was seen in AMB rejection capability. Frequency detection: Marked variation was also seen, with some stethoscopes performing better for different ranges (eg, cardiac) vs others (eg, gastrointestinal).Conclusion: The acoustic properties of stethoscopes varied considerably in loudness, AMB rejection, and frequency response. Stethoscope choice should take into account clinical conditions to be auscultated and the noise level of the environment. Keywords: stethoscope, analysis, acoustic, noise, signal

We report on the observation of a nonlinear intensity dependence of the terahertz radiation-induced ratchet effects in bilayer graphene with asymmetric dual-grating gate lateral lattices. These nonlinear ratchet currents are studied in structures of two designs with dual-grating gates fabricated on top of boron nitride encapsulated bilayer graphene and beneath it. The strength and sign of the photocurrent can be controllably varied by changing the bias voltages applied to individual dual-grating subgates and the back gate. The current consists of contributions insensitive to the radiation's polarization state, defined by the orientation of the radiation electric field vector with respect to the dual-grating gate metal stripes, and the circular ratchet sensitive to the radiation helicity. We show that intense terahertz radiation results in a nonlinear intensity dependence caused by electron gas heating. At room temperature, the ratchet current saturates at high intensities of the order of hundreds to several hundreds of kW cm − 2 . At T = 4 K, the nonlinearity manifests itself at intensities that are one or two orders of magnitude lower; moreover, the photoresponse exhibits a complex dependence on the intensity, including a saturation and even a change of sign with increasing intensity. This complexity is attributed to the interplay of the Seebeck ratchet and the dynamic carrier-density redistribution, which feature different intensity dependencies and nonlinear behavior of the sample's conductivity induced by electron gas heating. The latter is demonstrated by studying the THz photoconductivity. Our study demonstrates that graphene-based asymmetric dual-grating gate devices can be used as terahertz detectors at room temperature over a wide dynamic range, spanning many orders of magnitude of terahertz radiation power. Therefore, their integration together with current-driven read-out electronics is attractive for the operation with high-power pulsed sources. [ABSTRACT FROM AUTHOR]

Strong information literacy, collaboration, and argumentation skills are essential to success in problem-based learning (PBL), and computer-based scaffolding plays a key role in helping students enhance these skills. As students search for information, identify root causes, and propose problem solutions, they are faced with choosing among alternatives that result in enhanced or diminished skill development. In this qualitative study, we use the agentic perspective of Bandura's social cognitive theory to examine how students' choices illuminate their priorities, values and perspectives with respect to PBL inquiry. Results indicate that when seeking evidence to support claims in a PBL setting, given the choice between teacher-provided resources and their own research, students choose teacher-provided resources. This supports Barrows' original assertion about PBL that students are more likely to develop important skills like information literacy, self-directed learning, and problem solving when instructors refrain from providing domain specific knowledge prior to PBL activities.

In this study, we investigated how high school credit recovery students worked in small groups and used computer-based scaffolds to conduct scientific inquiry in a problem-based learning unit centered on water quality. We examined how students searched for and evaluated information from different sources, and used evidence to support their claims. Data sources included screen recordings, interviews, scaffold trace data, and scaffold entry quality ratings. Findings indicate that many students struggled to use the scaffolding and did not fully respond to scaffold prompts. Collaboration within small groups was often inhibited by frequent absences, struggles using the scaffolding, desires to complete tasks quickly rather than thoroughly, and an expectation that the group leader address the questions. However, many groups followed the scientific inquiry process prompted by the scaffolding, and support for collaboration within the scaffolds led students to negotiate the meaning of water quality data, and this in turn led students to see water quality as a complex, rather than a binary, construct.

Access to healthcare is a requirement for human well-being that is constrained, in part, by the allocation of healthcare resources relative to the geographically dispersed human population.sup.1-3. Quantifying access to care globally is challenging due to the absence of a comprehensive database of healthcare facilities. We harness major data collection efforts underway by OpenStreetMap, Google Maps and academic researchers to compile the most complete collection of facility locations to date. Leveraging the geographically variable strengths of our facility datasets, we use an established methodology.sup.4 to characterize travel time to healthcare facilities in unprecedented detail. We produce maps of travel time with and without access to motorized transport, thus characterizing travel time to healthcare for populations distributed across the wealth spectrum. We find that just 8.9% of the global population (646 million people) cannot reach healthcare within one hour if they have access to motorized transport, and that 43.3% (3.16 billion people) cannot reach a healthcare facility by foot within one hour. Our maps highlight an additional vulnerability faced by poorer individuals in remote areas and can help to estimate whether individuals will seek healthcare when it is needed, as well as providing an evidence base for efficiently distributing limited healthcare and transportation resources to underserved populations both now and in the future. A global analysis generating high-resolution maps of travel time shows that 91.1% of the world's population can reach a hospital or clinic within an hour if they have access to motorized transportation, but only 56.7% can do so by walking, highlighting additional inequities for underserved populations accessing healthcare., Author(s): D. J. Weiss [sup.1] [sup.2] [sup.3] , A. Nelson [sup.4] , C. A. Vargas-Ruiz [sup.1] , K. Gligoric [sup.5] , S. Bavadekar [sup.6] , E. Gabrilovich [sup.6] , A. [...]

With increasing class sizes, teachers and facilitators alike hope for learning groups where students work together in self-contained and autonomous ways requiring reduced teacher support. Yet many instructors find the idea of developing independent learning in small groups to be elusive particularly in K-12 settings (Ertmer and Simons in "Interdiscip J Probl Based Learn" 1(1):5, doi:10.7771/1541-5015.1005, 2006; Simons and Klein in "Inst Sci" 35(1):41-72, 2007). Autonomy in small learning groups is actively promoted in many of the forms of problem-based learning (PBL). A PBL learning group is traditionally defined as students with tutor assigned to the group. However, as PBL is introduced into K-12 environments, the assumption of group autonomous functioning is tenuous for a variety of reasons. The purpose of this research is to determine the extent to which a K-12 PBL learning group functions in autonomous ways when a computer-based scaffold provides some student support normally provided by the teacher or tutor during a PBL environmental science unit. If a computer-based scaffold can successfully enable key elements of autonomous group functioning by supplying process level support normally provided by a tutor or teacher, K-12 teachers anxious to attempt PBL may be able to venture with greater confidence that they can provide multiple learning groups adequate support. Results suggest that a computer-based scaffold informed by Moore's transactional distance theory can promote process elements of autonomous group functioning.

Previous studies have paid little attention to teachers' self or collegial considerations when making decisions about their students, precisely their tendency to avoid being blamed for students' failure. When a teacher is blamed for a student's difficulties, her/his public image ('face') is threatened, and s/he and her/his colleagues can be expected to engage in 'facework.' This study examined blame attribution and facework in teachers' discussions of struggling students and how they shaped teacher collaborative decision-making. Through discourse analysis of 187 audio-recorded discussions in placement meetings in an Israeli secondary school, the study highlights teachers' tendency to attribute blame for students' failure to others (175 blame events), mainly their students (53% of the cases). Micro-ethnographic discourse analysis found that when teachers blamed each other (17%), individual and collective face-management played a central role in their decision-making processes and outcomes. We explored the social dynamics in these discussions, using one discussion to illustrate the management of blame, related face-threat and facework, and implications for decisions. The study indicates the need for attention to blame avoidance and face issues in teacher training and PD programs and guidelines on how to manage them. [ABSTRACT FROM AUTHOR]

Objective: To examine the association between mental health workforce supply and spatial clusters of high versus low incidence of youth suicide. Methods: A cross-sectional analysis of spatial suicide clusters in young Australians (aged 10–25) from 2016 to 2020 was conducted using the scan statistic and suicide data from the National Coronial Information System. Mental health workforce was extracted from the 2020 National Health Workforce Dataset by local government areas. The Geographic Index of Relative Supply was used to estimate low and moderate-to-high mental health workforce supply for clusters characterised by a high and low incidence of suicide (termed suicide hotspots and coldspots, respectively). Univariate and multivariate logistic regression was used to determine the association between suicide clusters and a range of sociodemographic characteristics including mental health workforce supply. Results: Eight suicide hotspots and two suicide coldspots were identified. The multivariate analysis showed low mental health workforce supply was associated with increased odds of being involved in a suicide hotspot (adjusted odds ratio = 8.29; 95% confidence interval = 5.20–13.60), followed by residential remoteness (adjusted odds ratio = 2.85; 95% confidence interval = 1.68–4.89), and illicit drug consumption (adjusted odds ratio = 1.97; 1.24–3.11). Both coldspot clusters occurred in areas with moderate-to-high mental health workforce supply. Conclusion: Findings highlight the potential risk and protective roles that mental health workforce supply may play in the spatial distributions of youth suicide clusters. These findings have important implications for the provision of postvention and the prevention of suicide clusters. [ABSTRACT FROM AUTHOR]

A deformation of the hard palate can occur in spinal muscular atrophy and leads to problems with feeding and swallowing in early childhood. An objective analysis of the palatal changes is therefore desirable for early treatment initiation. In this study, we investigate a deep learning approach to automatically detect deformation in endoscopic images which were collected in a prospective in-vivo study on 33 infants. Ratings of five different experts were used to quantify the deformation and to train our network. We investigate different network architectures and data set splits and achieve classification performances of up to 0.85 ± 0.05 when distinguishing between normal and deformation using the Efficient- Net architecture. This combination of endoscopic imaging and deep learning offers a first approach for the objective assessment of palatal changes.