Miracle-dz/UniFAR-FTUs huggingface dataset:
Activating Mucosal-Associated Invariant T Cells Induces a Broad Antitumor Response

In vitro evidence suggests mucosal-associated invariant T (MAIT) cells can have antitumor function. This study shows MAIT cells stimulated in vivo using 5-OP-RU and CpG orchestrate potent antitumor responses, suggesting these cells as potential targets for cancer immunotherapy. Mucosal-associated invariant T (MAIT) cells are MR1-restricted innate-like T cells that recognize non-peptide antigens including riboflavin derivates. Although in vitro–activated MAIT cells show antitumor activity, the in vivo role of MAIT cells in cancer is still unclear. Here, we have shown that MAIT cells have antitumor function in vivo when activated by a combination of the synthetic riboflavin synthesis pathway–derived antigen 5-OP-RU [5-(2-oxopropylideneamino)-6-D-ribitylaminouracil] and the Toll-like receptor 9 (TLR9) agonist CpG. Coadministration of 5-OP-RU and CpG induced strong systemic in vivo expansion and activation of MAIT cells with high CD69 expression, pronounced effector memory phenotype, and upregulated levels of effector molecules including IFNγ, granzyme B, and perforin. Activated and expanded MAITs induced a potent and broad antitumor immune response in murine models of liver metastasis and hepatocellular carcinoma, lung metastasis, and subcutaneous tumors in two different mouse strains. Such tumor inhibition was absent in MAIT-deficient Mr1−/− mice. CRISPR/Cas9-mediated MR1 knockout in tumor cells did not affect efficacy of this MAIT-directed immunotherapy, pointing toward an indirect mechanism of action. Our findings suggest that MAIT cells are an attractive target for cancer immunotherapy. See related Spotlight by Lantz, p. 996.
The essential role of recurrent processing for figure-ground perception in mice

Perceptual organization in mice depends on feedback from higher visual areas, with specific roles for VIP and SOM interneurons. The segregation of figures from the background is an important step in visual perception. In primary visual cortex, figures evoke stronger activity than backgrounds during a delayed phase of the neuronal responses, but it is unknown how this figure-ground modulation (FGM) arises and whether it is necessary for perception. Here, we show, using optogenetic silencing in mice, that the delayed V1 response phase is necessary for figure-ground segregation. Neurons in higher visual areas also exhibit FGM and optogenetic silencing of higher areas reduced FGM in V1. In V1, figures elicited higher activity of vasoactive intestinal peptide–expressing (VIP) interneurons than the background, whereas figures suppressed somatostatin-positive interneurons, resulting in an increased activation of pyramidal cells. Optogenetic silencing of VIP neurons reduced FGM in V1, indicating that disinhibitory circuits contribute to FGM. Our results provide insight into how lower and higher areas of the visual cortex interact to shape visual perception.
Cell adhesion molecules and vascular endothelial growth factor at the systemic and alveolar level in COVID-19 ARDS.

Markus K. Kristensen; MD; Ronni R. Plovsing, MD, PhD; Ronan M. G. Berg; MD, DMSc; Rikke Krogh Madsen, MD, PhD; Andreas Ronit, MD, PhD Department of Infectious Diseases 144, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark; Department of Anaesthesiology and Intensive Care, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark; Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark; Department of Clinical
Health professional’s exposure, attitude, and acceptance of drug promotion by industry representatives: A cross-sectional study in Ethiopia

Interactions between pharmaceutical companies and health care providers have long been an area of interest from ethical as well as scientific grounds. The information provided by those companies must be scientifically accurate and fair. The current study aimed to investigate the exposure, attitude, and training background of medical doctors and pharmacy professionals regarding drug promotional activities, and assess their acceptance of promotional gifts provided by pharmaceutical sales representatives. A cross-sectional study was conducted on medical doctors and pharmacy professionals working at Bahir Dar and Gondar cities, Amhara regional state, Ethiopia. Data were collected using a self-administered structured questionnaire and Statistical Package for Social Science (SPSS) version 26 was used for analysis. A Chi-square test was computed to investigate the presence of an association between the dependent and independent variables. A p-value of less than 0.05 was considered to declare significance at a 95% Confidence Interval (CI). A total of 105 health professionals, 81 pharmacy professionals, and 24 medical doctors have participated in the study. Above two-thirds of the respondents (69.5%) agreed that most talks sponsored by drug companies were helpful and educational. On the other hand, 39% of the respondents agreed and 47.6% disagreed that receiving gifts from pharmaceutical representatives will increase the chance that they will eventually sell or recommend the drug company’s products. The majority of the study participants (81%) preferred drug samples and stationery as appropriate gifts by pharmaceutical sales representatives. Significant gaps were found regarding the training of health professionals about the ethics of drug marketing and how to deal with pharmaceutical representatives. Policies aiming at restricting health care provider’s contacts with pharmaceutical companies during residency training along with incorporating gift restriction policies could bring significant improvements.
Effectiveness of virtual reality immersion on procedure-related pain and anxiety in outpatient pain clinic: an exploratory randomized controlled trial

Background The study investigated virtual reality (VR) immersion in alleviating procedure-related pain in patients with chronic pain undergoing fluoroscopy-guided minimally-invasive intervention in a prone position at an outpatient clinic. Methods In this prospective randomized controlled study, 38 patients undergoing lumbar sympathetic ganglion block were randomized into either the VR or the control group. In the VR group, procedure-related pain was controlled via infiltration of local anesthetics while watching a 30-minute VR hypnotic program. In the control group, the skin infiltration alone was used, with the VR device switched off. The primary endpoint was an 11-point score on the numerical rating scale, indicating procedure-related pain. Patients’ satisfaction with pain control, anxiety levels, the need for additional local anesthetics during the procedure, hemodynamic stability, and any adverse events were assessed. Results Procedure-related pain was significantly lower in the VR group (3.7 ± 1.4) than in the control group (5.5 ± 1.7; P = 0.002). Post-procedural anxiety was lower in the VR group than in the control group (P = 0.025), with a significant reduction from pre-procedural anxiety (P < 0.001). Although patients’ satisfaction did not differ significantly (P = 0.158) between the groups, a higher number of patients required additional local anesthetics in the control group (n = 13) than in the VR group (n = 4; P = 0.001). No severe adverse events occurred in either group during the study. Conclusions VR immersion can be safely used as a novel adjunct to reduce procedural pain and anxiety during fluoroscopic pain intervention.
Factors driving the compositional diversity of Apis mellifera bee venom from a Corymbia calophylla (marri) ecosystem, Southwestern Australia

Bee venom (BV) is the most valuable product harvested from honeybees ($30 - $300 USD per gram) but marginally produced in apiculture. Though widely studied and used in alternative medicine, recent efforts in BV research have focused on its therapeutic and cosmetic applications, for the treatment of degenerative and infectious diseases. The protein and peptide composition of BV is integral to its bioactivity, yet little research has investigated the ecological factors influencing the qualitative and quantitative variations in the BV composition. Bee venom from Apis mellifera ligustica (Apidae), collected over one flowering season of Corymbia calophylla (Myrtaceae; marri) was characterized to test if the protein composition and amount of BV variation between sites is influenced by i) ecological factors (temperature, relative humidity, flowering index and stage, nectar production); ii) management (nutritional supply and movement of hives); and/or iii) behavioural factors. BV samples from 25 hives across a 200 km-latitudinal range in Southwestern Australia were collected using stimulatory devices. We studied the protein composition of BV by mass spectrometry, using a bottom-up proteomics approach. Peptide identification utilised sequence homology to the A. mellifera reference genome, assembling a BV peptide profile representative of 99 proteins, including a number of previously uncharacterised BV proteins. Among ecological factors, BV weight and protein diversity varied by temperature and marri flowering stage but not by index, this latter suggesting that inter and intra-year flowering index should be further explored to better appreciate this influence. Site influenced BV protein diversity and weight difference in two sites. Bee behavioural response to the stimulator device impacted both the protein profile and weight, whereas management factors did not. Continued research using a combination of proteomics, and bio-ecological approaches is recommended to further understand causes of BV variation in order to standardise and improve the harvest practice and product quality attributes.
Receptor for Advanced Glycation Endproducts: A Multiligand Receptor of the Immunoglobulin Superfamily

Receptor for Advanced Glycation Endproducts: A Multiligand Receptor of the Immunoglobulin Superfamily Receptor for advanced glycation endproducts (RAGE), a member of the immunoglobulin superfamily of cell surface molecules, was originally discovered for its ability to bind to and transduce the biological effects of advanced glycation endproducts (AGEs), which accumulate in settings such as hyperglycemia, aging, inflammation, renal failure, and oxidative stress. AGEs are an heterogeneous group of modified molecules, which form particularly on lysine and arginine amino acid residues. Among the AGEs, one of the most prevalent species found in human subjects with diabetes mellitus, the carboxymethyl lysine (CML) AGEs are signal transduction ligands of RAGE. The key to the biology of RAGE lies in its diverse ligand families. The discovery that RAGE bound non-AGE ligands linked the receptor indelibly to mechanisms important in the inflammatory response. Beyond AGEs, RAGE is also a signal transduction receptor for molecules such as members of the S100/calgranulin family, high mobility group box-1, Mac1, and lysophosphatidic acid. Hence, RAGE and its ligands accumulate in the nondiabetic state and to enhanced degrees in diabetes mellitus, at least in part on account of the potent effects of hyperglycemia on stimulating increased formation and accumulation of RAGE ligand AGEs. AGEs, and other ligands, through RAGE comprise a unique family that imbues chronic inflammatory stress as their chief biological action, for example, through sustained activation of the proinflammatory transcription factor nuclear factor-κB. Furthermore, RAGE action downregulates mRNA transcript and protein and activity levels of Glo1 (or glyoxalase 1). GLO1, which detoxifies the pre-AGE intermediate, methylglyoxal, is a defense against increased AGE production. The finding that RAGE downregulates Glo1 underscores the possibility that RAGE is at the center of a feedforward loop regulating both ligand activity and ligand levels. In this context, the finding that RAGE sustains chronic inflammatory cues stimulated by its ligands provides further fuel for sustaining production and accumulation of proinflammatory RAGE ligands, which may be escorted into inflammatory sites through S100/calgranulin-bearing or high mobility group box-1–bearing immune cells.
The End of Corticosteroid in Sepsis : Fragile Results From Fragile Trials

REFERENCES 1. Riem R, Lakhal K: Will This Patient Need to Be Admitted to the ICU After Supratentoral Brain Tumor Resection? A Hard Nut to Crack. Crit Care Med 2018; 46:e1226–e1227 2. Franko LR, Hollon T, Linzey J, et al: Clinical factors associated with ICU-specific care following supratentoral brain tumor resection and validation of a risk prediction score. Crit Care Med 2018; 46:1302–1308 3. Nates JL, Nunnally M, Kleinpell R, et al: ICU admission, discharge, and triage guidelines: A framework to enhance clinical operations, development of institutional policies, and further research. Crit Care Med 2016; 44:1553–1602 4. Florman JE, Cushing D, Keller LA, et al: A protocol for postoperative admission of elective craniotomy patients to a non-ICU or step-down setting. J Neurosurg 2017; 127:1392–1397 DOI: 10.1097/CCM.0000000000003455
Gastric Polyposis Syndromes

Most gastric polyps are fundic gland polyps and hyperplastic polyps. Adenomas, inflammatory fibroid polyps, and neuroendocrine tumors are other types of gastric polyps that occur less frequently. Rarely, a gastric polyp may be associated with a syndrome, including hereditary cancer syndromes. Some of these syndromes are also associated with an increased risk of gastric cancer. We present a case of a 50-year-old woman with known Cowden syndrome who presents with multiple gastric hamartomatous polyps. We then review the clinical, endoscopic, and pathologic features of various syndromes that are associated with gastric polyps. Fundic gland polyp–predominant syndromes include familial adenomatous polyposis, gastric adenocarcinoma and proximal polyposis of the stomach, and MUTYH-associated polyposis, all of which are hereditary cancer syndromes. Gastric hamartomatous polyps are found in patients with juvenile polyposis syndrome, Peutz-Jeghers syndrome, PTEN hamartoma tumor syndrome including Cowden syndrome, and Cronkhite-Canada syndrome. Syndromic gastric polyps may be biopsied in patients with a previously established diagnosis of the underlying syndrome, such as surveillance endoscopies in familial adenomatous polyposis. On other occasions, the pathologic assessment of gastric polyps may prompt or contribute to a diagnostic workup of an underlying syndrome in conjunction with other clinical and endoscopic findings.
Supporting Teachers’ Implementation of Classroom-Based Physical Activity

The increasing evidence about CBPA ’ s benefits for students indicates that it should be considered a best practice for elementary schools (2,3). However, given the low prevalence of use across the nation, it seems warranted to mo-bilize efforts to increase the number of classroom teachers who use CBPA and the consistency with which they do so. Yet, many questions remain about how best to encourage teachers ’ implementation of CBPA. This article reviews previous work exploring teacher-level implementation, including consideration of how CBPA implementation is measured and what is known about factors associated with implementation. We discuss interventions and potential innovations to support increased rates of implementation and sustained use of CBPA among classroom teachers. Our review of published evidence is supplemented with examples from our own work over the past 4 yr on the Physically Active Classrooms Energize! (PACE) project at Boise State University, which is supported by a research grant from the Institute of Education Sciences. On the PACE project, ABSTRACT Research exploring factors related to teachers ’ implementation of classroom-based physical activity (CBPA) has increased in recent years. This article highlights key findings from the literature about the implementation and maintenance of CBPA by classroom teachers. The authors provide an overview of the literature examining CBPA implementation from an implementation science perspective. Topics addressed include methods for measuring implementation, characteristics of CBPA resources, and predictors of teachers ’ implementation of CBPA. Findings from the narrative review are presented in tandem with insights from the authors ’ work during a grant-funded project examining strategies to improve CBPA implementation in elementary schools. Many off-the-shelf resources for CBPA implementation exist, with varying degrees of implementation support. Studies have used a variety of methods to measure implementation, mostly focused on teacher self-report. Few studies have provided evidence regarding long-term use of CBPA, but those that do report decreased implementation rates over time. A robust body of research examining CBPA implementation facilitators and barriers shows that organizational-level support from district and school administrators is crucial for successful implementation. Leadership buy-in is crucial for the implementation of policies and practices in schools, such as CBPA initiatives. Approaches that are embedded within school systems, such as communities of practice and coaching from school champions, have potential for improving implementation. designed implementation to increase how many teachers within a school provide regular CBPA to their students in the recommended To organize these findings, we use a framework for con- ceptualizing the implementation of CBPA in classrooms.
Money Creation in Decentralized Finance: A Dynamic Model of Stablecoin and Crypto Shadow Banking

Stablecoins rise to meet the demand for safe assets in decentralized finance. Stablecoin issuers transform risky reserve assets into tokens of stable values, deploying a variety of tactics. To address the questions on the viability of stablecoins, regulations, and the initiatives led by large platforms, we develop a dynamic model of optimal stablecoin management and characterize an instability trap. The system is bimodal: stability can last for a long time, but once stablecoins break the buck following negative shocks, volatility persists. Debasement triggers a vicious cycle but is unavoidable as it allows efficient risk sharing between the issuer and stablecoin users.
Establishment of National Public Audit Oversight Boards and Audit Quality

We examine the establishment of public audit oversight bodies (POB) around the world. While there is substantial evidence on the impacts of the U.S. PCAOB, generalizability of the PCAOB experience to other countries establishing POBs is not a foregone conclusion. We provide descriptive evidence on the establishment of POBs including characteristics of the POBs and factors associated with the timing of establishment up through 2020. Using a difference-in-differences research design over a 20-year period, we find that establishment of a POB is associated with improvements in audit quality. This association is driven by countries that committed to public oversight earlier in our time-series and only for those early POBs that mandate reporting of inspection results or have enforcement authority. This paper contributes to our understanding of public audit oversight and provides important nuance to the relation between POBs and audit quality.
What Makes a Good Image? Airbnb Demand Analytics Leveraging Interpretable Image Features

We study how Airbnb property demand changed after the acquisition of verified images (taken by Airbnb’s photographers) and explore what makes a good image for an Airbnb property. Using deep learning and difference-in-difference analyses on an Airbnb panel dataset spanning 7,423 properties over 16 months, we find that properties with verified images had 8.98% higher occupancy than properties without verified images (images taken by the host). To explore what constitutes a good image for an Airbnb property, we quantify 12 human-interpretable image attributes that pertain to three artistic aspects—composition, color, and the figure-ground relationship—and we find systematic differences between the verified and unverified images. We also predict the relationship between each of the 12 attributes and property demand, and we find that most of the correlations are significant and in the theorized direction. Our results provide actionable insights for both Airbnb photographers and amateur host photographers who wish to optimize their images. Our findings contribute to and bridge the literature on photography and marketing (e.g., staging), which often either ignores the demand side (photography) or does not systematically characterize the images (marketing).
Credit ratings, regulatory arbitrage and systemic risk

This study investigates how credit rating based capital regulation instigates systemic risk. To safeguard the financial system European banks and insurance corporations face stringent capital requirements based on credit ratings to prevent excessive risk taking. Building on prior literature, we estimate the extent to which credit ratings accurately reflect credit risk. We use a confidential granular dataset with bond-level portfolio holdings from 2013Q4 to 2019Q4. First, we find that credit rating based capital regulation incentivizes banks and insurance corporations to hold more bonds with inflated credit ratings, while this effect is absent for investors who do not face capital requirements based on credit ratings. Second, banks and insurance corporations are especially inclined to hoard bonds with inflated credit ratings that carry substantial systematic risk. Third, bonds with inflated credit ratings instigate larger fire-sales after credit rating downgrades which affect required regulatory capital. Finally, the least capitalized banks and insurance corporations are most inclined to effectively reduce their required regulatory capital by holding bonds with inflated credit ratings. Consequently, our findings suggest that credit rating based capital regulation amplifies unanticipated systemic risk and financial fragility through hoarding bonds with inflated credit ratings.
Is Journalistic Truth Dead? Measuring How Informed Voters Are about Political News

To investigate general patterns in news information in the United States, we combine a protocol for identifying major political news stories, 11 monthly surveys with 15,000 participants, and a model of news discernment. When confronted with a true and a fake news story, 47 percent of subjects confidently choose the true story, 3 percent confidently choose the fake story, and the remaining half are uncertain. Socioeconomic differences are associated with large variations in the probability of selecting the true news story. Partisan congruence between an individual and a news story matters, but its impact is up to an order of magnitude smaller. (JEL D72, D83, L82)
Corporate Social Responsibility Culture and International M&As

Abstract We examine the role of corporate culture in M&As by utilizing a unique corporate social responsibility (CSR) dataset, providing in-depth information on multiple dimensions of organizational culture in 22 developed markets. In accordance with the prediction of the culture clash theory, a wider divergence between the CSR corporate cultures of the acquiring and target firms is associated with lower acquirer announcement and long-run returns as well as synergistic gains for the combined firm. Cultural misalignment also increases the time required to finalise a deal, reduces the likelihood of deal completion and the percentage of stock payment. Our results are robust to alternative explanations (e.g., similarities in national culture, acquirer CSR performance, institutional configurations), different regression specifications, and additional cultural misalignment measures. Our findings highlight the importance of the need for a deeper understanding of the role of CSR for the target selection process, integration planning, and financing choice of M&As to corporations and their investors.