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Introduction There have been increasing efforts to integrate the arts and humanities into medical education, particularly during undergraduate medical education (UME). Previous studies, however, have focused on courses and curricular programming without rigorous characterization of the associated paracurricular environment or infrastructure enabling or facilitating these offerings. Methods To assess opportunities for students to engage the arts and humanities during their medical education as well as the institutional resources to support those opportunities, we developed the Humanities and Arts Programming Scale (HARPS): an 18-point scale involving eight sub-domains (Infrastructure, Curricular Opportunities, Extracurricular Engagement, Opportunities for Immersion, Faculty Engagement, Staff Support, Student Groups, and Scholarship). This scale was used to evaluate the top-31 ranked United States medical schools as determined by US News and World Report’s (USWNR) Medical School Research Rankings using information derived from public-facing, online information. Results Mean cumulative HARPS score was 11.26, with a median score of 12, a standard deviation of 4.32 and a score range of 3–17. Neither USWNR ranking nor private/public institution status were associated with the cumulative score (p = 0.121, p = 0.739). 52% of institutions surveyed had a humanities-focused center/division with more than 70% of the schools having significant (> 5) faculty engaged in the medical humanities. 65% of schools offered 10 or more paracurricular medical humanities events annually, while 68% of the institutions had more than 5 medical humanities student organizations. While elective, non-credit courses are available, only 3 schools required instruction in the arts and humanities, and comprehensive immersive experiences in the medical humanities were present in only 29% of the schools. Conclusions Although there is a significant presence of the medical humanities in UME, there is a need for integration of the arts and humanities into required UME curricula and into immersive pathways for engaging the medical humanities.

This paper describes the Medical Humanities Council (MHC), a student-led initiative to promote the health humanities at the Perelman School of Medicine (PSOM) at the University of Pennsylvania. Building on data-focused advocacy, peer benchmarking, and collaboration with curricular leaders, the MHC has become the cornerstone of a sustainable and flourishing health humanities infrastructure and programming targeted at medical students at PSOM. The MHC illustrates how student advocacy can advance the arts and humanities and serves as a model for student-led promotion of the health humanities, particularly when programing and/or institutional support are lacking.

There have been increasing efforts to integrate the arts and humanities into medical education, particularly during undergraduate medical education (UME). Previous studies, however, have focused on courses and curricular programming without rigorous characterization of the associated paracurricular environment or infrastructure enabling or facilitating these offerings. To assess opportunities for students to engage the arts and humanities during their medical education as well as the institutional resources to support those opportunities, we developed the Humanities and Arts Programming Scale (HARPS): an 18-point scale involving eight sub-domains (Infrastructure, Curricular Opportunities, Extracurricular Engagement, Opportunities for Immersion, Faculty Engagement, Staff Support, Student Groups, and Scholarship). This scale was used to evaluate the top-31 ranked United States medical schools as determined by US News and World Report's (USWNR) Medical School Research Rankings using information derived from public-facing, online information. Mean cumulative HARPS score was 11.26, with a median score of 12, a standard deviation of 4.32 and a score range of 3-17. Neither USWNR ranking nor private/public institution status were associated with the cumulative score (p = 0.121, p = 0.739). 52% of institutions surveyed had a humanities-focused center/division with more than 70% of the schools having significant (> 5) faculty engaged in the medical humanities. 65% of schools offered 10 or more paracurricular medical humanities events annually, while 68% of the institutions had more than 5 medical humanities student organizations. While elective, non-credit courses are available, only 3 schools required instruction in the arts and humanities, and comprehensive immersive experiences in the medical humanities were present in only 29% of the schools. Although there is a significant presence of the medical humanities in UME, there is a need for integration of the arts and humanities into required UME curricula and into immersive pathways for engaging the medical humanities.

The timing of her departure coincides with claims that Mrs [Irina Abramovich] has engaged the celebrity divorce lawyer Raymond Tooth, of the firm Sears Tooth. A spokesman for Mr Abramovich denied this. If Abramovich v Abramovich ever went to court it would be the biggest divorce in English legal history, if not in the world, lawyers said yesterday. \"No member of the Abramovich family has filed suit for divorce, nor have they retained the law firm of Sears Tooth or any other law firm regarding a possible divorce,'' he said. \"Suggestions that the Abramovichs are facing serious difficulties are similarly untrue.''

The current practice for diagnosis of COVID-19, based on SARS-CoV-2 PCR testing of pharyngeal or respiratory specimens in a symptomatic patient at high epidemiologic risk, likely underestimates the true prevalence of infection. Serologic methods can more accurately estimate the disease burden by detecting infections missed by the limited testing performed to date. Here, we describe the validation of a coronavirus antigen microarray containing immunologically significant antigens from SARS-CoV-2, in addition to SARS-CoV, MERS-CoV, common human coronavirus strains, and other common respiratory viruses. A comparison of antibody profiles detected on the array from control sera collected prior to the SARS-CoV-2 pandemic versus convalescent blood specimens from virologically confirmed COVID-19 cases demonstrates near complete discrimination of these two groups, with improved performance from use of antigen combinations that include both spike protein and nucleoprotein. This array can be used as a diagnostic tool, as an epidemiologic tool to more accurately estimate the disease burden of COVID-19, and as a research tool to correlate antibody responses with clinical outcomes. COVID-19 diagnosis is commonly performed by PCR testing, however, serologic methods are more accurate and versatile for monitoring disease burden and epidemiology. Here the authors report a protein microarray with antigens from SARS-CoV-2, SARS-CoV, MERS-CoV as well as common human respiratory viruses.

Bone-resorbing osteoclasts significantly contribute to osteoporosis and bone metastases of cancer. MicroRNAs play important roles in physiology and disease, and present tremendous therapeutic potential. Nonetheless, how microRNAs regulate skeletal biology is underexplored. Here we identify miR-34a as a novel and critical suppressor of osteoclastogenesis, bone resorption and the bone metastatic niche. miR-34a is downregulated during osteoclast differentiation. Osteoclastic miR-34a-overexpressing transgenic mice exhibit lower bone resorption and higher bone mass. Conversely, miR-34a knockout and heterozygous mice exhibit elevated bone resorption and reduced bone mass. Consequently, ovariectomy-induced osteoporosis, as well as bone metastasis of breast and skin cancers, are diminished in osteoclastic miR-34a transgenic mice, and can be effectively attenuated by miR-34a nanoparticle treatment. Mechanistically, we identify transforming growth factor-β-induced factor 2 (Tgif2) as an essential direct miR-34a target that is pro-osteoclastogenic. Tgif2 deletion reduces bone resorption and abolishes miR-34a regulation. Together, using mouse genetic, pharmacological and disease models, we reveal miR-34a as a key osteoclast suppressor and a potential therapeutic strategy to confer skeletal protection and ameliorate bone metastasis of cancers.

Idiopathic pulmonary fibrosis (IPF) is a progressive and life threatening disease with median survival of 2.5-3 years. The IPF lung is characterized by abnormal lung remodeling, epithelial cell hyperplasia, myofibroblast foci formation, and extracellular matrix deposition. Analysis of gene expression microarray data revealed that cartilage oligomeric matrix protein (COMP), a non-collagenous extracellular matrix protein is among the most significantly up-regulated genes (Fold change 13, p-value <0.05) in IPF lungs. This finding was confirmed at the mRNA level by nCounter® expression analysis in additional 115 IPF lungs and 154 control lungs as well as at the protein level by western blot analysis. Immunohistochemical analysis revealed that COMP was expressed in dense fibrotic regions of IPF lungs and co-localized with vimentin and around pSMAD3 expressing cells. Stimulation of normal human lung fibroblasts with TGF-β1 induced an increase in COMP mRNA and protein expression. Silencing COMP in normal human lung fibroblasts significantly inhibited cell proliferation and negatively impacted the effects of TGF-β1 on COL1A1 and PAI1. COMP protein concentration measured by ELISA assay was significantly increased in serum of IPF patients compared to controls. Analysis of serum COMP concentrations in 23 patients who had prospective blood draws revealed that COMP levels increased in a time dependent fashion and correlated with declines in force vital capacity (FVC). Taken together, our results should encourage more research into the potential use of COMP as a biomarker for disease activity and TGF-β1 activity in patients with IPF. Hence, studies that explore modalities that affect COMP expression, alleviate extracellular matrix rigidity and lung restriction in IPF and interfere with the amplification of TGF-β1 signaling should be persuaded.

Toxoplasma gondii commonly infects humans and while most infections are controlled by the immune response, currently approved drugs are not capable of clearing chronic infection in humans. Hence, approximately one third of the world’s human population is at risk of reactivation, potentially leading to severe sequelae. To identify new candidates for treating chronic infection, we investigated a series of compounds derived from diversity-oriented synthesis. Bicyclic azetidines are potent low nanomolar inhibitors of phenylalanine tRNA synthetase (PheRS) in T. gondii , with excellent selectivity. Biochemical and genetic studies validate PheRS as the primary target of bicyclic azetidines in T. gondii , providing a structural basis for rational design of improved analogs. Favorable pharmacokinetic properties of a lead compound provide excellent protection from acute infection and partial protection from chronic infection in an immunocompromised mouse model of toxoplasmosis. Collectively, PheRS inhibitors of the bicyclic azetidine series offer promise for treatment of chronic toxoplasmosis. Current treatments for toxoplasmosis are limited by adverse reactions and inability to cure chronic infections dominated by semi-dormant cyst forms. Here the authors demonstrate the potential of small molecule inhibitors of PheRS for controlling acute and chronic toxoplasmosis.

Force platforms and 3-dimensional motion-capture systems provide an accurate method of quantifying postural stability. Substantial cost, space, time to administer, and need for trained personnel limit widespread use of biomechanical techniques in the assessment of postural stability in clinical or field environments. To determine whether accelerometer and gyroscope data sampled from a consumer electronics device (iPad2) provide sufficient resolution of center-of-gravity (COG) movements to accurately quantify postural stability in healthy young people. Controlled laboratory study. Research laboratory in an academic medical center. A total of 49 healthy individuals (age = 19.5 ± 3.1 years, height = 167.7 ± 13.2 cm, mass = 68.5 ± 17.5 kg). Participants completed the NeuroCom Sensory Organization Test (SOT) with an iPad2 affixed at the sacral level. Primary outcomes were equilibrium scores from both systems and the time series of the angular displacement of the anteroposterior COG sway during each trial. A Bland-Altman assessment for agreement was used to compare equilibrium scores produced by the NeuroCom and iPad2 devices. Limits of agreement was defined as the mean bias (NeuroCom - iPad) ± 2 standard deviations. Mean absolute percentage error and median difference between the NeuroCom and iPad2 measurements were used to evaluate how closely the real-time COG sway measured by the 2 systems tracked each other. The limits between the 2 devices ranged from -0.5° to 0.5° in SOT condition 1 to -2.9° to 1.3° in SOT condition 5. The largest absolute value of the measurement error within the 95% confidence intervals for all conditions was 2.9°. The mean absolute percentage error analysis indicated that the iPad2 tracked NeuroCom COG with an average error ranging from 5.87% to 10.42% of the NeuroCom measurement across SOT conditions. The iPad2 hardware provided data of sufficient precision and accuracy to quantify postural stability. Accuracy, portability, and affordability make using the iPad2 a reasonable approach for assessing postural stability in clinical and field environments.

The transcription factor SOX2 is an essential regulator of pluripotent stem cells and promotes development and maintenance of squamous epithelia. We previously reported that SOX2 is an oncogene and subject to highly recurrent genomic amplification in squamous cell carcinomas (SCCs). Here, we have further characterized the function of SOX2 in SCC. Using ChIP-seq analysis, we compared SOX2-regulated gene profiles in multiple SCC cell lines to ES cell profiles and determined that SOX2 binds to distinct genomic loci in SCCs. In SCCs, SOX2 preferentially interacts with the transcription factor p63, as opposed to the transcription factor OCT4, which is the preferred SOX2 binding partner in ES cells. SOX2 and p63 exhibited overlapping genomic occupancy at a large number of loci in SCCs; however, coordinate binding of SOX2 and p63 was absent in ES cells. We further demonstrated that SOX2 and p63 jointly regulate gene expression, including the oncogene ETV4, which was essential for SOX2-amplified SCC cell survival. Together, these findings demonstrate that the action of SOX2 in SCC differs substantially from its role in pluripotency. The identification of the SCC-associated interaction between SOX2 and p63 will enable deeper characterization the downstream targets of this interaction in SCC and normal squamous epithelial physiology.