tbuckley/cabot-search huggingface dataset:
Successful Treatment of Interstitial Lung Disease in STAT3 Gain-of-Function Using JAK Inhibitors
Authors: Manuel Silva-Carmona, Tiphanie P. Vogel, Sarah Marchal, Myriam Guesmi, Jean-Christophe Dubus, Sylvie Leroy, Alexandre Fabre, Vincent Barlogis, Lisa R. Forbes, Lisa Giovannini-Chami
Journal: American Journal of Respiratory and Critical Care Medicine (2020)
Metabolic Pathways That Control Skin Homeostasis and Inflammation
Authors: Danay Cibrian, Hortensia de la Fuente, Francisco Sánchez-Madrid
Journal: Trends in Molecular Medicine (2020)

Keratinocytes and skin immune cells are actively metabolizing nutrients present in their microenvironment. This is particularly important in common chronic inflammatory skin diseases such as psoriasis and atopic dermatitis, characterized by hyperproliferation of keratinocytes and expansion of inflammatory cells, thus suggesting increased cell nutritional requirements. Proliferating inflammatory cells and keratinocytes express high levels of glucose transporter (GLUT)1, l-type amino acid transporter (LAT)1, and cationic amino acid transporters (CATs). Main metabolic regulators such as hypoxia-inducible factor (HIF)-1α, MYC, and mechanistic target of rapamycin (mTOR) control immune cell activation, proliferation, and cytokine release. Here, we provide an updated perspective regarding the potential role of nutrient transporters and metabolic pathways that could be common to immune cells and keratinocytes, to control psoriasis and atopic dermatitis.
Dissecting RoomDecisions to withhold treatmentLife, Death and DecisionsDoctors and Nurses Reflect on Neonatal Practice, Hazel McCaffey, Peter Fowler, Books for Midwives, Altrincham, UK (1996), Pp 294. £18.95, ISBN: 1-898507-55-4
Authors: Anne Greenough
Journal: The Lancet (1997)
Estimating number of cases and spread of coronavirus disease (COVID-19) using critical care admissions, United Kingdom, February to March 2020
Authors: Mark Jit, Thibaut Jombart, Emily S Nightingale, Akira Endo, Sam Abbott, W John Edmunds
Journal: Eurosurveillance (2020)

An exponential growth model was fitted to critical care admissions from two surveillance databases to determine likely coronavirus disease (COVID-19) case numbers, critical care admissions and epidemic growth in the United Kingdom before the national lockdown. We estimate, on 23 March, a median of 114,000 (95% credible interval (CrI): 78,000-173,000) new cases and 258 (95% CrI: 220-319) new critical care reports, with 527,000 (95% CrI: 362,000-797,000) cumulative cases since 16 February.
Is that all there is? Or is chimpanzees group hunt “fair” enough?
Authors: Angelica Kaufmann
Journal: Behavioral and Brain Sciences (2020)

Abstract Tomasello claims that we lack convincing evidence that nonhuman animals manifest a sense of moral obligation (i.e., the concept of fairness) in their group activities. The philosophical analysis of distinctive evidence from ethology, namely group hunting practices among chimpanzees, can help the author appreciate the distinctive character of this behaviour as a display of fairness put into practice.
Single-Cell Transcriptome Analysis Reveals Intratumoral Heterogeneity in ccRCC, which Results in Different Clinical Outcomes
Authors: Junyi Hu, Zhaohui Chen, Lin Bao, Lijie Zhou, Yaxin Hou, Lilong Liu, Ming Xiong, Yuhan Zhang, Bin Wang, Zhen Tao, Ke Chen
Journal: Molecular Therapy (2020)

Clear-cell renal cell carcinoma (ccRCC) is the most common histological type of RCC. To investigate the intratumoral heterogeneity of ccRCC, we analyzed single-cell RNA-sequencing data and identified 15 major cell types, along with 39 subgroups of cells derived from tumor or non-malignant tissues, and confirmed their presence by immunofluorescence staining in tissue chips. In this study, we verified that T cell exhaustion was the key factor responsible for the immunosuppressive property of ccRCC tissues, which was significantly related to poor prognosis. We also found that abnormal metabolic patterns occurred not only in cancer cells, but also in tumor-infiltrating stromal cells. Based on the fraction of each cell cluster detected by CIBERSORTx, 533 patients from The Cancer Genome Atlas (TCGA) KIRC dataset were divided into three groups. One group, which showed a lesser proportion of activated CD8+ cells and greater proportion of exhausted CD8+ cells, was associated with a poor prognosis. Hence, the blockade of immunosuppressive checkpoints, not only PD-1, but also LAG3, TIM-3, and other inhibitory checkpoints, could serve as a potential target for ccRCC immunotherapy. Our work will further the understanding of the heterogeneity among ccRCC tissues and provide novel strategies for treating ccRCC. Clear-cell renal cell carcinoma (ccRCC) is the most common histological type of RCC. To investigate the intratumoral heterogeneity of ccRCC, we analyzed single-cell RNA-sequencing data and identified 15 major cell types, along with 39 subgroups of cells derived from tumor or non-malignant tissues, and confirmed their presence by immunofluorescence staining in tissue chips. In this study, we verified that T cell exhaustion was the key factor responsible for the immunosuppressive property of ccRCC tissues, which was significantly related to poor prognosis. We also found that abnormal metabolic patterns occurred not only in cancer cells, but also in tumor-infiltrating stromal cells. Based on the fraction of each cell cluster detected by CIBERSORTx, 533 patients from The Cancer Genome Atlas (TCGA) KIRC dataset were divided into three groups. One group, which showed a lesser proportion of activated CD8+ cells and greater proportion of exhausted CD8+ cells, was associated with a poor prognosis. Hence, the blockade of immunosuppressive checkpoints, not only PD-1, but also LAG3, TIM-3, and other inhibitory checkpoints, could serve as a potential target for ccRCC immunotherapy. Our work will further the understanding of the heterogeneity among ccRCC tissues and provide novel strategies for treating ccRCC.
COVID-19 and biologics for psoriasis: A high-epidemic area experience—Bergamo, Lombardy, Italy
Authors: Andrea Carugno, Daniele Mario Gambini, Francesca Raponi, Pamela Vezzoli, Andrea Gustavo C. Locatelli, Marco Di Mercurio, Elisa Robustelli Test, Paolo Sena
Journal: Journal of the American Academy of Dermatology (2020)
A Nutrient-Sensing Transition at Birth Triggers Glucose-Responsive Insulin Secretion
Authors: Aharon Helman, Andrew L. Cangelosi, Jeffrey C. Davis, Quan Pham, Arielle Rothman, Aubrey L. Faust, Juerg R. Straubhaar, David M. Sabatini, Douglas A. Melton
Journal: Cell Metabolism (2020)

A drastic transition at birth, from constant maternal nutrient supply in utero to intermittent postnatal feeding, requires changes in the metabolic system of the neonate. Despite their central role in metabolic homeostasis, little is known about how pancreatic β cells adjust to the new nutritional challenge. Here, we find that after birth β cell function shifts from amino acid- to glucose-stimulated insulin secretion in correlation with the change in the nutritional environment. This adaptation is mediated by a transition in nutrient sensitivity of the mTORC1 pathway, which leads to intermittent mTORC1 activity. Disrupting nutrient sensitivity of mTORC1 in mature β cells reverts insulin secretion to a functionally immature state. Finally, manipulating nutrient sensitivity of mTORC1 in stem cell-derived β cells in vitro strongly enhances their glucose-responsive insulin secretion. These results reveal a mechanism by which nutrients regulate β cell function, thereby enabling a metabolic adaptation for the newborn.
Elevated serum interleukin-8 is associated with enhanced intratumor neutrophils and reduced clinical benefit of immune-checkpoint inhibitors
Authors: Kurt A. Schalper, Michael Carleton, Ming Zhou, Tian Chen, Ye Feng, Shu-Pang Huang, Alice M. Walsh, Vipul Baxi, Dimple Pandya, Timothy Baradet, Darren Locke, Qiuyan Wu, Timothy P. Reilly, Penny Phillips, Venkata Nagineni, Nicole Gianino, Jianlei Gu, Hongyu Zhao, Jose Luis Perez-Gracia, Miguel F. Sanmamed, Ignacio Melero
Journal: Nature Medicine (2020)
Plant-Provided Food for Carnivorous Insects: A Protective Mutualism and its Applications, Felix L. Wäckers, Paul C.J. van Rijn, Jan Bruin (Eds.). Cambridge University Press (2005), US$130.00/£75.00 hbk (356 pages), ISBN: 0521819415
Authors: Aaron M. Ellison
Journal: Trends in Ecology & Evolution (2006)
Developmental Relationships of Four Exhausted CD8+ T Cell Subsets Reveals Underlying Transcriptional and Epigenetic Landscape Control Mechanisms
Authors: Jean-Christophe Beltra, Sasikanth Manne, Mohamed S. Abdel-Hakeem, Makoto Kurachi, Josephine R. Giles, Zeyu Chen, Valentina Casella, Shin Foong Ngiow, Omar Khan, Yinghui Jane Huang, Patrick Yan, Kito Nzingha, Wei Xu, Ravi K. Amaravadi, Xiaowei Xu, Giorgos C. Karakousis, Tara C. Mitchell, Lynn M. Schuchter, Alexander C. Huang, E. John Wherry
Journal: Immunity (2020)
Proton pump inhibitors are associated with increased risk of alopecia areata: A nationwide nested case-control study
Authors: Cheng-Yuan Li, Ying-Xiu Dai, Yun-Ting Chang, Ya-Mei Bai, Shih-Jen Tsai, Tzeng-Ji Chen, Mu-Hong Chen
Journal: Journal of the American Academy of Dermatology (2020)
Loss of Cardiac Ferritin H Facilitates Cardiomyopathy via Slc7a11-Mediated Ferroptosis
Authors: Xuexian Fang, Zhaoxian Cai, Hao Wang, Dan Han, Qi Cheng, Pan Zhang, Feng Gao, Yingying Yu, Zijun Song, Qian Wu, Peng An, Sicong Huang, Jianwei Pan, Hou-Zao Chen, Jinghai Chen, Andreas Linkermann, Junxia Min, Fudi Wang
Journal: Circulation Research (2020)

Maintaining iron homeostasis is essential for proper cardiac function. Both iron deficiency and iron overload are associated with cardiomyopathy and heart failure via complex mechanisms. Although ferritin plays a central role in iron metabolism by storing excess cellular iron, the molecular function of ferritin in cardiomyocytes remains unknown.To characterize the functional role of Fth (ferritin H) in mediating cardiac iron homeostasis and heart disease.Mice expressing a conditional Fth knockout allele were crossed with 2 distinct Cre recombinase-expressing mouse lines, resulting in offspring that lack Fth expression specifically in myocytes (MCK-Cre) or cardiomyocytes (Myh6-Cre). Mice lacking Fth in cardiomyocytes had decreased cardiac iron levels and increased oxidative stress, resulting in mild cardiac injury upon aging. However, feeding these mice a high-iron diet caused severe cardiac injury and hypertrophic cardiomyopathy, with molecular features typical of ferroptosis, including reduced glutathione (GSH) levels and increased lipid peroxidation. Ferrostatin-1, a specific inhibitor of ferroptosis, rescued this phenotype, supporting the notion that ferroptosis plays a pathophysiological role in the heart. Finally, we found that Fth-deficient cardiomyocytes have reduced expression of the ferroptosis regulator Slc7a11, and overexpressing Slc7a11 selectively in cardiomyocytes increased GSH levels and prevented cardiac ferroptosis.Our findings provide compelling evidence that ferritin plays a major role in protecting against cardiac ferroptosis and subsequent heart failure, thereby providing a possible new therapeutic target for patients at risk of developing cardiomyopathy.
Effects of the COVID-19 Pandemic on Routine Pediatric Vaccine Ordering and Administration — United States, 2020
Authors: Jeanne M. Santoli, Megan C. Lindley, Malini B. DeSilva, Elyse O. Kharbanda, Matthew F. Daley, Lisa Galloway, Julianne Gee, Mick Glover, Ben Herring, Yoonjae Kang, Paul Lucas, Cameron Noblit, Jeanne Tropper, Tara Vogt, Eric Weintraub
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

the president of the United States declared a national emergency in response to the coronavirus disease 2019 (COVID-19) pandemic (1).With reports of laboratory-confirmed cases in all 50 states by that time (2), disruptions were anticipated in the U.S. health care system's ability to continue providing routine preventive and other nonemergency care.In addition, many states and localities issued shelter-in-place or stay-at-home orders to reduce the spread of COVID-19, limiting movement outside the home to essential activities (3).On March 24, CDC posted guidance emphasizing the importance of routine well child care and immunization, particularly for children aged ≤24 months, when many childhood vaccines are recommended.*Two data sources were examined to assess the impact of the pandemic on pediatric vaccination in the United States: Vaccines for Children Program (VFC) provider order data from CDC's Vaccine Tracking System and Vaccine Safety Datalink (VSD) vaccine administration data.Vaccination coverage is the traditional metric used to assess vaccine usage; however, provider orders and doses administered represent two immediately available proxy measures.VFC is a national program that provides federally purchased vaccines to approximately 50% of U.S. children aged 0-18 years.† Cumulative doses of VFC-funded vaccines ordered by health care providers at weekly intervals during two periods (January 7, 2019-April 21, 2019 [period 1] and January 6, 2020-April 19, 2020 [period 2]) were tallied, and differences in cumulative weekly vaccine doses ordered between period 2 and period 1 were calculated for all noninfluenza vaccines § that the Advisory Committee on Immunization Practices (ACIP) recommends for children and, as an example, * https://www.cdc.gov/coronavirus/2019-ncov/hcp/pediatric-hcp.html.
Abstract 112: Microrna-532-5p Protects the Mouse Heart Against Myocardial Infarction by Repressing a Positive Regulator of Endothelial-to-mesenchymal Transition, Prss23
Authors: Ahmed S Bayoumi, Jian P Teoh, Il-man Kim
Journal: Circulation Research (2016)

Myocardial infarction (MI) leads to cardiac remodeling and development of heart failure. Insufficient myocardial capillary density after MI has been identified as a critical event in this process. MicroRNAs (miRs), negative regulators of gene expression, have emerged as important players in heart diseases including MI. We previously showed that miR-532-5p (miR-532) is up-regulated by the β-arrestin-biased β-blocker carvedilol (Carv), which activates protective pathways in the heart independent of G protein-mediated second messenger signaling (Figure A-B). Here, we test whether a β2-adrenergic receptor (β2AR)/β-arrestin-responsive miR, miR-532 functions as a cardioprotective miR against MI. Using cultured cardiac endothelial cell (CEC) and in vivo approaches in mice, we demonstrate that knockdown of miR-532 induces CEC apoptosis when subjected to simulated ischemia-reperfusion. In vivo blocking of miR-532 via intramyocardial injection of its locked nucleic acid-anti-miR results in post-MI abnormalities in cardiac function and remodeling. Mechanistically, miR-532 promotes cardiac vascularization after MI in part by repressing a predicted target, Prss23 and subsequently activating endothelial cell markers such as CD-31 (Figure C). Prss23, which is a vascular protease and modulates Snail transcription to promote endothelial-to-mesenchymal transition (EndoMT), is also down-regulated by Carv in mouse hearts. In conclusion, our novel findings indicate that miR-532-Prss23 axis acts as an important regulator of CEC function during MI and can be suitable for therapeutic intervention in the setting of ischemic heart disease.
Development of tissue factor-targeted liposomes for effective drug delivery to stroma-rich tumors
Authors: Kosuke Shimizu, Yoshihito Takeuchi, Kazuma Otsuka, Tomoya Mori, Yudai Narita, Shohei Takasugi, Yasuhiro Magata, Yasuhiro Matsumura, Naoto Oku
Journal: Journal of Controlled Release (2020)
Lung Development Genes and Adult Lung Function
Authors: Laura Portas, Miguel Pereira, Seif O. Shaheen, Annah B. Wyss, Stephanie J. London, Peter G. J. Burney, Matthew Hind, Charlotte H. Dean, Cosetta Minelli
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Rationale: Poor lung health in adult life may occur partly through suboptimal growth and development, as suggested by epidemiological evidence pointing to early life risk factors.Objectives: To systematically investigate the effects of lung development genes on adult lung function.Methods: Using UK Biobank data, we tested the association of 391 genes known to influence lung development with FVC and FEV1/FVC. We split the dataset into two random subsets of 207,616 and 138,411 individuals, using the larger subset to select the most promising signals and the smaller subset for replication.Measurements and Main Results: We identified 55 genes, of which 36 (16 for FVC, 19 for FEV1/FVC, and one for both) had not been identified in the largest, most recent genome-wide study of lung function. Most of these 36 signals were intronic variants; expression data from blood and lung tissue showed that the majority affect the expression of the genes they lie within. Further testing of 34 of these 36 signals in the CHARGE and SpiroMeta consortia showed that 16 replicated after Bonferroni correction and another 12 replicated at nominal significance level. Of the 55 genes, 53 fell into four biological categories whose function is to regulate organ size and cell integrity (growth factors; transcriptional regulators; cell-to-cell adhesion; extracellular matrix), suggesting that these specific processes are important for adult lung health.Conclusions: Our study demonstrates the importance of lung development genes in regulating adult lung function and influencing both restrictive and obstructive patterns. Further investigation of these developmental pathways could lead to druggable targets.
Reply to Chang and Yew
Authors: Giovanni Sotgiu, Giovanni Battista Migliori, Dick Menzies, Sundari Mase, Terence Chorba, Barbara Seaworth, Payam Nahid
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Author(s): Sotgiu, Giovanni; Battista Migliori, Giovanni; Menzies, Dick; Mase, Sundari; Chorba, Terence; Seaworth, Barbara; Nahid, Payam
An Agent Independent Axis for Executed and Modeled Choice in Medial Prefrontal Cortex
Authors: Antoinette Nicolle, Miriam C. Klein-Flügge, Laurence T. Hunt, Ivo Vlaev, Raymond J. Dolan, Timothy E.J. Behrens
Journal: Neuron (2013)

(Neuron 75, 1114–1121; September 20, 2012) As the result of a journal error during the production process, an incorrect version of the Supplemental Information was previously published with this article online. We have now corrected the online Supplemental Information and apologize for the error. An Agent Independent Axis for Executed and Modeled Choice in Medial Prefrontal CortexNicolle et al.NeuronSeptember 20, 2012In BriefNicolle et al. show that valuation and choice for self and other exhibit parallel computations, where gradients exist within both medial prefrontal and temporoparietal cortices. Ventral regions compute choices that will be executed, while dorsal regions compute choices that are merely modeled. Full-Text PDF Open Access
Term complications and subsequent risk of preterm birth: registry based study
Authors: Liv G Kvalvik, Allen J Wilcox, Rolv Skjærven, Truls Østbye, Quaker E Harmon
Journal: BMJ (2020)

Abstract Objective To explore conditions and outcomes of a first delivery at term that might predict later preterm birth. Design Population based, prospective register based study. Setting Medical Birth Registry of Norway, 1999-2015. Participants 302 192 women giving birth (live or stillbirth) to a second singleton child between 1999 and 2015. Main outcome measures Main outcome was the relative risk of preterm delivery (&lt;37 gestational weeks) in the birth after a term first birth with pregnancy complications: pre-eclampsia, placental abruption, stillbirth, neonatal death, and small for gestational age. Results Women with any of the five complications at term showed a substantially increased risk of preterm delivery in the next pregnancy. The absolute risks for preterm delivery in a second pregnancy were 3.1% with none of the five term complications (8202/265 043), 6.1% after term pre-eclampsia (688/11 225), 7.3% after term placental abruption (41/562), 13.1% after term stillbirth (72/551), 10.0% after term neonatal death (22/219), and 6.7% after term small for gestational age (463/6939). The unadjusted relative risk for preterm birth after term pre-eclampsia was 2.0 (95% confidence interval 1.8 to 2.1), after term placental abruption was 2.3 (1.7 to 3.1), after term stillbirth was 4.2 (3.4 to 5.2), after term neonatal death was 3.2 (2.2 to 4.8), and after term small for gestational age was 2.2 (2.0 to 2.4). On average, the risk of preterm birth was increased 2.0-fold (1.9-fold to 2.1-fold) with one term complication in the first pregnancy, and 3.5-fold (2.9-fold to 4.2-fold) with two or more complications. The associations persisted after excluding recurrence of the specific complication in the second pregnancy. These links between term complications and preterm delivery were also seen in the reverse direction: preterm birth in the first pregnancy predicted complications in second pregnancies delivered at term. Conclusions Pre-eclampsia, placental abruption, stillbirth, neonatal death, or small for gestational age experienced in a first term pregnancy are associated with a substantially increased risk of subsequent preterm delivery. Term complications seem to share important underlying causes with preterm delivery that persist from pregnancy to pregnancy, perhaps related to a mother’s predisposition to disorders of placental function.