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\"Maps are rarely given the same attention as other print media or art forms in urban history. Author Min Kyung Lee shows their rich potential in this lavishly illustrated study, which brings together maps and other archival materials along with drawings and paintings. She works across disciplines to examine mapping practices in the development of nineteenth-century Paris and the transformative role that urban mapping had on the city's modernization. Lee investigates Paris's formation as a modern city, ultimately framing the practice of cartography as a catalyst for the emergence of new spatial and compositional theories.\" -- Provided by publisher.

•Various kinds of misinformation are related to specific types of vaccine hesitancy-related attitude.•Misinformation based in politics, religion, and media is related to various types of vaccine hesitancy.•Medical and scientific information is not sufficient to combat COVID-19 vaccine hesitancy. COVID-19 vaccine hesitancy has emerged as a major public health challenge. Although medical and scientific misinformation has been known to fuel vaccine hesitancy in the past, misinformation surrounding COVID-19 seems to be rampant, and increasing evidence suggests that it is contributing to COVID-19 vaccine hesitancy today. The relationship between misinformation and COVID-19 vaccine hesitancy is complex, however, and it is relatively understudied. In this article, we report qualitative data from two related but distinct studies from a larger project. Study 1 included semi-structured, open-ended interviews conducted in October–November 2020 via phone with 30 participants to investigate the relationship between misinformation and COVID-19 vaccine hesitancy. Study 1′s results then informed the design of open-ended questions for Study 2, an online survey conducted in May–June 2021 to consider the relationship between misinformation and vaccine hesitancy further. The data were examined with thematic analysis. Study 1 led to the identification of positive and negative themes related to attitudes toward COVID-19 vaccines. In Study 2, responses from vaccine-hesitant participants included six categories of misinformation: medical, scientific, political, media, religious, and technological. Across both Study 1 and Study 2, six vaccine hesitancy themes were identified from the data: concerns about the vaccines’ future effects, doubts about the vaccines’ effectiveness, commercial profiteering, preference for natural immunity, personal freedom, and COVID-19 denial. The relationship between misinformation and vaccine hesitancy is complicated. Various types of misinformation exist, with each related to a specific type of vaccine hesitancy-related attitude. Personal freedom and COVID-19 denial are vaccine attitudes of particular interest, representing important yet understudied phenomena. Medical and scientific approaches may not be sufficient to combat misinformation based in religion, media, or politics; and public health officials may benefit from partnering with experts from those fields to address harmful misinformation that is driving COVID-19 vaccine hesitancy.

Dental measurements have been commonly taken from plaster dental models obtained from alginate impressions can. Through the use of an intraoral scanner, digital impressions now acquire the information directly from the mouth. The purpose of this study was to determine the validity of the intraoral scans compared to plaster models. Two types of dental models (intraoral scan and plaster model) of 20 subjects were included in this study. The subjects had impressions taken of their teeth and made as plaster model. In addition, their mouths were scanned with the intraoral scanner and the scans were converted into digital models. Eight transverse and 16 anteroposterior measurements, 24 tooth heights and widths were recorded on the plaster models with a digital caliper and on the intraoral scan with 3D reverse engineering software. For 3D surface analysis, the two models were superimposed by using best-fit algorithm. The average differences between the two models at all points on the surfaces were computed. Paired t-test and Bland-Altman plot were used to determine the validity of measurements from the intraoral scan compared to those from the plaster model. There were no significant differences between the plaster models and intraoral scans, except for one measurement of lower intermolar width. The Bland-Altman plots of all measurements showed that differences between the two models were within the limits of agreement. The average surface difference between the two models was within 0.10 mm. The results of the present study indicate that the intraoral scans are clinically acceptable for diagnosis and treatment planning in dentistry and can be used in place of plaster models.

Single-cell transcriptome profiling of tumour tissue isolates allows the characterization of heterogeneous tumour cells along with neighbouring stromal and immune cells. Here we adopt this powerful approach to breast cancer and analyse 515 cells from 11 patients. Inferred copy number variations from the single-cell RNA-seq data separate carcinoma cells from non-cancer cells. At a single-cell resolution, carcinoma cells display common signatures within the tumour as well as intratumoral heterogeneity regarding breast cancer subtype and crucial cancer-related pathways. Most of the non-cancer cells are immune cells, with three distinct clusters of T lymphocytes, B lymphocytes and macrophages. T lymphocytes and macrophages both display immunosuppressive characteristics: T cells with a regulatory or an exhausted phenotype and macrophages with an M2 phenotype. These results illustrate that the breast cancer transcriptome has a wide range of intratumoral heterogeneity, which is shaped by the tumour cells and immune cells in the surrounding microenvironment. Genetic heterogeneity in breast cancer has been demonstrated at a single-cell resolution with high levels of genome coverage. Here, the authors perform transcriptome analysis of 515 single cells from 11 patients and define core gene expression signatures for subtype-specific single breast cancer cells and tumour-infiltrating immune cells.

Using an ORF kinome screen in MCF-7 cells treated with the CDK4/6 inhibitor ribociclib plus fulvestrant, we identified FGFR1 as a mechanism of drug resistance. FGFR1-amplified/ER+ breast cancer cells and MCF-7 cells transduced with FGFR1 were resistant to fulvestrant ± ribociclib or palbociclib. This resistance was abrogated by treatment with the FGFR tyrosine kinase inhibitor (TKI) lucitanib. Addition of the FGFR TKI erdafitinib to palbociclib/fulvestrant induced complete responses of FGFR1-amplified/ER+ patient-derived-xenografts. Next generation sequencing of circulating tumor DNA (ctDNA) in 34 patients after progression on CDK4/6 inhibitors identified FGFR1/2 amplification or activating mutations in 14/34 (41%) post-progression specimens. Finally, ctDNA from patients enrolled in MONALEESA-2, the registration trial of ribociclib, showed that patients with FGFR1 amplification exhibited a shorter progression-free survival compared to patients with wild type FGFR1. Thus, we propose breast cancers with FGFR pathway alterations should be considered for trials using combinations of ER, CDK4/6 and FGFR antagonists. Era+ breast cancer patients often develop resistance to endocrine therapy. Here, the authors show that FGFR1 amplification is a resistance mechanism to CDK4/6 inhibitor and endocrine therapy and that combined treatment with FGFR, CDK4/6, and anti-estrogens is a potential therapeutic strategy in Era+ breast cancer tumors.

We investigated the relationship of changes in Metabolic syndrome (MetS) and its components with the risk of type 2 diabetes (T2D) in South Korea. Records of 10,806,716 adults aged ≥ 20 years without a history of T2D between 2009 and 2015 were retrieved from database of the South Korean National Health Insurance Service and analyzed. Changes in metabolic components were monitored over a two-year period with follow-up occurring at an average of 4.087 years. During the follow-up period, 848,859 individuals were diagnosed with T2D. The risk of diabetes was lowered with a decrease in the number of MetS components at baseline and the second visit ( p for trend <0.0001). Multivariable-adjusted HRs for incident diabetes were 0.645 among individuals with reduced number of MetS components, 0.54 for those with improvement in elevated fasting glucose, 0.735 for those with improvement in elevated triglycerides, 0.746 for those with improvement in elevated blood pressure, 0.763 for those with improvement in reduced HDL-cholesterol, and 0.92 for those with improvement in abdominal obesity compared with those manifesting them at both time points. In conclusion, changes in metabolic syndrome and its components were significantly associated with the development of T2D. Improvement in MetS and its components attenuated the risk of diabetes.

The aim of this study is to evaluate upper airway changes three-dimensionally following rapid maxillary expansion (RME) and compare the changes with matched controls. Seventeen patients (mean age 12.6 ± 1.8 years) with maxillary transverse deficiency were treated with RME. Using the propensity score matching method, 17 patients (mean age 12.3 ± 1.5 years) were selected from a non-RME control group of 33. Case-control matching was performed based on 5 covariates: age, gender, CBCT scan interval, sagittal skeletal pattern, and tongue posture. Airway volumes of nasopharynx and oropharynx and minimum cross-sectional areas (MCA) of oropharynx were measured and compared between the case and control groups in CBCT scan images. In the case group, significant increases from before to after RME were found in all measurements except MCA of the retroglossal segment of oropharynx. Before treatment, there were no significant differences between case group and control group. While comparing the case group with the control group after treatment showed overall greater increases in the case group. In particular, MCA of retropalatal segment showed statistically significant differences. The results of this study indicate that RME causes an increase in upper airway dimensions.

Background Addition of CDK4/6 inhibitors (CDK4/6i) to endocrine therapy significantly increased progression-free survival, leading to their approval and incorporation into the metastatic breast cancer treatment paradigm. With these inhibitors being routinely used for patients with advanced estrogen receptor-positive (ER+) breast cancer, resistance to these agents and its impact on subsequent therapy needs to be understood. Considering the central role of ER in driving the growth of ER+ breast cancers, and thus endocrine agents being a mainstay in the treatment paradigm, the effects of prior CDK4/6i exposure on ER signaling and the relevance of ER-targeted therapy are important to investigate. The objective of this study was to evaluate the anti-tumor activity of elacestrant, a novel oral selective estrogen receptor degrader (SERD), in preclinical models of CDK4/6i resistance. Methods Elacestrant was evaluated as a single agent, and in combination with alpelisib or everolimus, in multiple in vitro models and patient-derived xenografts that represent acquired and “de novo” CDK4/6i resistance. Results Elacestrant demonstrated growth inhibition in cells resistant to all three approved CDK4/6i (palbociclib, abemaciclib, ribociclib) in both ESR1 wild-type and mutant backgrounds. Furthermore, we demonstrated that elacestrant, as a single agent and in combination, inhibited growth of patient-derived xenografts that have been derived from a patient previously treated with a CDK4/6i or exhibit de novo resistance to CDK4/6i. While the resistant lines demonstrate distinct alterations in cell cycle modulators, this did not affect elacestrant’s anti-tumor activity. In fact, we observe that elacestrant downregulates several key cell cycle players and halts cell cycle progression in vitro and in vivo. Conclusions We demonstrate that breast cancer tumor cells continue to rely on ER signaling to drive tumor growth despite exposure to CDK4/6i inhibitors. Importantly, elacestrant can inhibit this ER-dependent growth despite previously reported mechanisms of CDK4/6i resistance observed such as Rb loss, CDK6 overexpression, upregulated cyclinE1 and E2F1, among others. These data provide a scientific rationale for the evaluation of elacestrant in a post-CDK4/6i patient population. Additionally, elacestrant may also serve as an endocrine backbone for rational combinations to combat resistance.

ObjectiveTo compare the accuracy of complete-arch scans and quadrant scans obtained using a direct chairside intraoral scanner.Material and methodsIntraoral scans were obtained from 20 adults without missing teeth except for the third molar. Maxillary and mandibular complete-arch scans were carried out, and 4 quadrant scans for each arch were performed to obtain right posterior, right anterior, left anterior, and left posterior quadrant scans. Complete-arch scans and quadrant scans were compared with corresponding model scans using best-fit surface-based registration. Shell/shell deviations were computed for complete-arch scans and quadrant scans and compared between the complete-arch scans and each quadrant scans. In addition, shell/shell deviations were calculated also for each individual tooth in complete-arch scans to evaluate factors which influence the accuracy of intraoral scans.ResultsComplete-arch scans showed relatively greater errors (0.09 ~ 0.10 mm) when compared to quadrant scans (0.05 ~ 0.06 mm). The errors were greater in the maxillary scans than in the mandibular scans. The evaluation of errors for each tooth showed that the errors were greater in posterior teeth than in anterior teeth. Comparing the right and left errors, the right side posterior teeth showed a more substantial variance than the left side in the mandibular scans.ConclusionThe scanning accuracy has a difference between complete-arch scanning and quadrant scanning, particularly in the posterior teeth. Careful consideration is needed to avoid scanning inaccuracy for maxillary or mandibular complete-arch, particularly in the posterior area because a complete-arch scan might have potential error than a quadrant scan.

This study explores the implications of the flipped classroom experiment in South Korea as a counter-proposal for the school innovation project based on the Korean educational context. Using Dongpyung middle school in South Korea for this case study, this paper focuses on how and why the flipped classroom impacts Korea's education culture. The results of the experiment provide significant insights, such as promoting more active classroom learning and the improvement of student academic achievement. In particular, the narratives of the students and teachers in the flipped classroom experiment show the following positive impacts on learning and teaching: (1) Transformation into a more equal and democratic classroom, (2) restoration of enjoyment in learning and teaching, (3) improvement of self-confidence, and (4) inspiration for the learning and teaching community. Based on these results, this paper discusses possible implications of the flipped classroom as an alternative future class model in Korean society.