tbuckley/cabot-search huggingface dataset:
Abstract 11301: Empagliflozin Early Reverses Metabolic and Cardiac Disturbances in Type-2 Diabetics With Chronic Heart Failure and Reduces Hospitalization for Heart Failure
Authors: Tatsuaki Murakami, Kazuo Ohsato
Journal: Circulation (2018)

Introduction: Although diabetes mellitus is associated with excess of worsening heart failure, effective therapies in patients with diabetes mellitus and chronic heart failure have not been establi...
Objective responses to first-line neoadjuvant carboplatin–paclitaxel regimens for ovarian, fallopian tube, or primary peritoneal carcinoma (ICON8): post-hoc exploratory analysis of a randomised, phase 3 trial
Authors: Robert D Morgan, Iain A McNeish, Adrian D Cook, Elizabeth C James, Rosemary Lord, Graham Dark, Rosalind M Glasspool, Jonathan Krell, Christine Parkinson, Christopher J Poole, Marcia Hall, Dolores Gallardo-Rincón, Michelle Lockley, Sharadah Essapen, Jeff Summers, Anjana Anand, Abel Zachariah, Sarah Williams, Rachel Jones, Kate Scatchard, Axel Walther, Jae-Weon Kim, Sudha Sundar, Gordon C Jayson, Jonathan A Ledermann, Andrew R Clamp
Journal: The Lancet Oncology (2020)
Pharmacologic Activation of LXR Alters the Expression Profile of Tumor-Associated Macrophages and the Abundance of Regulatory T Cells in the Tumor Microenvironment
Authors: José M. Carbó, Theresa E. León, Joan Font-Díaz, Juan Vladimir De la Rosa, Antonio Castrillo, Felix R. Picard, Daniel Staudenraus, Magdalena Huber, Lídia Cedó, Joan Carles Escolà-Gil, Lucía Campos, Latifa Bakiri, Erwin F. Wagner, Carme Caelles, Thomas Stratmann, Jo A. Van Ginderachter, Annabel F. Valledor
Journal: Cancer Research (2020)

Liver X receptors (LXR) are transcription factors from the nuclear receptor family that are activated by oxysterols and synthetic high-affinity agonists. In this study, we assessed the antitumor effects of synthetic LXR agonist TO901317 in a murine model of syngeneic Lewis Lung carcinoma. Treatment with TO901317 inhibited tumor growth in wild-type, but not in LXR-deficient mice, indicating that the antitumor effects of the agonist depends on functional LXR activity in host cells. Pharmacologic activation of the LXR pathway reduced the intratumoral abundance of regulatory T cells (Treg) and the expression of the Treg-attracting chemokine Ccl17 by MHCIIhigh tumor-associated macrophages (TAM). Moreover, gene expression profiling indicated a broad negative impact of the LXR agonist on other mechanisms used by TAM for the maintenance of an immunosuppressive environment. In studies exploring the macrophage response to GM-CSF or IL4, activated LXR repressed IRF4 expression, resulting in subsequent downregulation of IRF4-dependent genes including Ccl17. Taken together, this work reveals the combined actions of the LXR pathway in the control of TAM responses that contribute to the antitumoral effects of pharmacologic LXR activation. Moreover, these data provide new insights for the development of novel therapeutic options for the treatment of cancer. SIGNIFICANCE: This study reveals unrecognized roles of LXR in the transcriptional control of the tumor microenvironment and suggests use of a synthetic LXR agonist as a novel therapeutic strategy to stimulate antitumor activity.
SETBP1 and NRAS Mutations Are Frequent Events in Post-Myeloproliferative Neoplasm Acute Myeloid Leukemia (post-MPN AML) Lacking JAK-STAT Activating Mutations
Authors: Kamal Menghrajani, Franck Rapaport, Caroline Jane McNamara, Sean M. Devlin, Christopher Famulare, Minal Patel, Juan Medina, Lonette Sandy, Heidi Kosiorek, Rona Singer Weinberg, Andrea Arruda, Jessica Schulman, Taghi Manshouri, Marina Kremyanskaya, John Mascarenhas, Ronald Hoffman, Vikas Gupta, Srdan Verstovsek, Ross L. Levine, Raajit K. Rampal
Journal: Blood (2017)
Demographic History and Genomic Response to Environmental Changes in a Rapid Radiation of Wild Rats
Authors: Deyan Ge, Anderson Feijó, Zhixin Wen, Alexei V Abramov, Liang Lu, Jilong Cheng, Shengkai Pan, Sicheng Ye, Lin Xia, Xuelong Jiang, Alfried P Vogler, Qisen Yang
Journal: Molecular Biology and Evolution (2020)

For organisms to survive and prosper in a harsh environment, particularly under rapid climate change, poses tremendous challenges. Recent studies have highlighted the continued loss of megafauna in terrestrial ecosystems and the subsequent surge of small mammals, such as rodents, bats, lagomorphs, and insectivores. However, the ecological partitioning of these animals will likely lead to large variation in their responses to environmental change. In the present study, we investigated the evolutionary history and genetic adaptations of white-bellied rats (Niviventer Marshall, 1976), which are widespread in the natural terrestrial ecosystems in Asia but also known as important zoonotic pathogen vectors and transmitters. The southeastern Qinghai-Tibet Plateau was inferred as the origin center of this genus, with parallel diversification in temperate and tropical niches. Demographic history analyses from mitochondrial and nuclear sequences of Niviventer demonstrated population size increases and range expansion for species in Southeast Asia, and habitat generalists elsewhere. Unexpectedly, population increases were seen in N. eha, which inhabits the highest elevation among Niviventer species. Genome scans of nuclear exons revealed that among the congeneric species, N. eha has the largest number of positively selected genes. Protein functions of these genes are mainly related to olfaction, taste, and tumor suppression. Extensive genetic modification presents a major strategy in response to global changes in these alpine species.
Myocardial protection by heparin-based coacervate of FGF10
Authors: Zhouguang Wang, Yan Huang, Yan He, Sinan Khor, Xingxing Zhong, Jian Xiao, Qingsong Ye, Xiaokun Li
Journal: Bioactive Materials (2020)

Heart disease is still the leading killer all around the world, and its incidence is expected to increase over the next decade. Previous reports have already shown the role of fibroblast growth factor10 (FGF10) in alleviating heart diseases. However, FGF10 has not been used to treat heart diseases because the free protein has short half-life and low bioactivity. Here, an injectable coacervate was designed to protect growth factor from degradation during delivery and the effects of the FGF10 coacervate were studied using a mice acute myocardial infarction (MI) model. As shown in our echocardiographic results, a single injection of FGF10 coacervate effectively inhibited preserved cardiac contractibility and ventricular dilation when compared with free FGF10 and the saline treatment 6 weeks after MI. It is revealed in histological results that the MI induced myocardial inflammation and fibrosis was reduced after FGF10 coacervate treatment. Furthermore, FGF10 coacervate treatment could improve arterioles and capillaries stabilization through increasing the proliferation of endothelial and mural cells. However, with the same dosage, no statistically significant difference was shown between free FGF10, heparin+FGF10 and saline treatment, especially in long term. On another hand, FGF10 coacervate also increased the expression of cardiac-associated the mRNA (cTnT, Cx43 and α-SMA), angiogenic factors (Ang-1 and VEGFA) and decreased the level of inflammatory factor (tumor necrosis factor-α). The downstream signaling of the FGF10 was also investigated, with the western blot results showing that FGF10 coacervate activated the p-FGFR, PI3K/Akt and ERK1/2 pathways to a more proper level than free FGF10 or heparin+FGF10. In general, it is revealed in this research that one-time injection of FGF10 coacervate sufficiently attenuated MI induced injury when compared with an equal dose of free FGF10 or heparin+FGF10 injection.
Who Is the <i>Parasite</i>?—COVID-19 and Structural Narratives of Health Inequity
Authors: Nina Y. Hu
Journal: JAMA (2020)

This Arts and Medicine feature reviews Parasite, winner of the 2020 Academy Award for Best Picture, finding in its story of class struggle a way for clinicians and health systems to better understand structural origins of patients' socioeconomic disadvantage and health inequity.
Covid-19: Chaotic decision making and failure to communicate undermined government response, says report
Authors: Shaun Griffin
Journal: BMJ (2020)

Ministers must improve the way they use and communicate advice from scientists or risk repeating mistakes made earlier in the coronavirus pandemic, a think tank has warned.

A report from the Institute for Government outlined a series of errors it said the government made in the past 10 months: from the lack of a coherent strategy when lockdown restrictions were lifted in May to its failure to consult scientists on “epidemiologically illiterate” policies, such as the “Eat Out to Help Out” scheme, and its delay in consulting the Scientific Advisory Group for Emergencies on the return of students to universities.1

Many such problems had been seen in the government’s handling of past crises, such as the outbreaks of bovine spongiform encephalopathy, foot and mouth disease, and H1N1 “swine” flu, said the report. These included the blurring …
Covid-19: Order to reschedule and delay second vaccine dose is “totally unfair,” says BMA
Authors: Elisabeth Mahase
Journal: BMJ (2020)

Covid-19: Order to reschedule and delay second vaccine dose "totally unfair," says BMA Elisabeth MahaseHealthcare workers in England have been told to reschedule appointments for the second dose of the Pfizer and BioNTech covid-19 vaccine after the government's advisory committee decided that vaccinating as many people as possible with a first dose should be the priority.
Improved cancer phototheranostic efficacy of hydrophobic IR780 via parenteral route by association with tetrahedral nanostructured DNA
Authors: Shuo Wang, Zengyi Liu, Yue Tong, Yunqian Zhai, Xiujie Zhao, Xinmin Yue, Yanqi Qiao, Yonghui Liu, Yongmei Yin, Rimo Xi, Wei Zhao, Meng Meng
Journal: Journal of Controlled Release (2020)
Bridging Office-Based Care with the Virtual Practice Care Model: Evolving Care for CKD Patients in the COVID-19 Pandemic—and Beyond
Authors: Bingbin Zhao, Lei Zhang, Peili Ji, Jianfeng Lin, Jianfang Han, Jiaying Li, Zijuan Zhou, Haiyun Wang, Xia Hong, Winfred W. Williams, Limeng Chen
Journal: Journal of the American Society of Nephrology (2020)

Background: Since the outbreak of the coronavirus epidemic, the 'virtual' telemedicine has become a critical substitute for patient-provider interactions  However, virtual encounters often face challenges in care for high-risk patients such as chronic kidney disease (CKD) patients  In this study, we explore the patient's satisfaction and practical effects of a newly established telemedicine program in CKD patients' care during the pandemic  Methods: We established an online CKD patient care program, including triage strategy, medical care delivery, and psychological support, based on a smartphone application  A total of 278 CKD patients were invited, at least 3 months before the pandemic or during the pandemic  A pilot survey interrogating medical and psychologicalconditions was conducted  The feedback to the program and the psychological assessment repeated after one month  Results: Totally, 181 patients showed active responses to the program, with 289 person-time medical consultations occurred during the study  The virtual care program provided a rapid triage, with 17% patients provided a timely referral to in-patient medical encounters  Nearly all patients (97 4%) believed the program was helpful  The number of symptoms (OR 1 309, 95%CI 1 113-1 541;P=0 001) and being enrolled during pandemic (OR 3 939, 95% CI 1 174-13 221;P=0 026) were associated with high stress  After the follow-up, the high-stress CKD group at baseline showed a significant decrease in avoidance score (6 9±4 7 vs  9 8±1 9, P=0 015)  Conclusions: During the pandemic, we established an online telemedicine care program for CKD patients that provides a rapid triage function, effective CKD disease management, and essential psychological support
Low‐dose oral minoxidil improves global hair density and length in children with loose anagen hair syndrome
Authors: R. Jerjen, W.‐L. Koh, R. Sinclair, B. Bhoyrul
Journal: British Journal of Dermatology (2020)

Loose anagen hair syndrome (LAHS) is a sporadic or autosomal dominant hair disorder which typically affects girls aged 2-6 years. 1 It is characterised by increased hair shedding,
IGFBP4 inhibits IGF1 driven tumour cell proliferation and VEGF expression
Authors: Anthony J. Ryan, Dermot Mc Brierty, David Bouchier-Hayes, Judith H. Harmey
Journal: Cancer Research (2004)

4339  Insulin like growth factors (IGFs) play key roles in growth, development, cellular transformation and survival of malignant cells. Bioavailability of IGFs is regulated by the IGF binding proteins (IGFBPs), which bind IGFs. IGF release is dependent on cleavage of the IGFBPs by their proteases. There is conflicting data on the significance of IGF and IGFBP expression in tumour growth. We examined the expression of IGFBP4 and its recently identified protease pregnancy associated plasma protein A (PAPP-A), in normal and tumour mouse tissues and 4T1.2 mammary adenocarcinoma cells by Western blotting. The effects of wild type IGF1 and recombinant mutant IGF1, which is resistant to IGFBP binding (IGF1(RE)), were examined on proliferation of 4T1.2 cells. 4T1.2 cells over express IGFBP4 but not PAPP-A. IGF1 at of 50, 100, 500, 1000, and 2000ng/ml did not stimulate proliferation of 4T1.2 cells whereas IGF1 (RE) at 50, 100, 500, 1000, and 2000ng/ml, increased proliferation of these cells (p
Abstract 16016: Pregnancy Loss and Cardiovascular Disease Risk: A 20-Year Prospective Study
Authors: Tomas Cabeza De Baca, Eva M Durazo, Robert J Glynn, Jonathan Z Butler, Julie E Buring, Michelle A Albert
Journal: Circulation (2018)

Background: Although pregnancy outcomes affect cardiovascular disease risk (CVD), long-term prospective data related to pregnancy loss and CVD risk is limited, particularly in United States populat...
Head‐to‐head comparison of biologics in psoriasis: better acceleration does not necessarily win all races
Authors: L. Puig
Journal: British Journal of Dermatology (2020)

Linked Article: Blauvelt et al. Br J Dermatol 2021; 184:1047–1058. L.P. has received consultancy/speaker's honoraria from and/or participated in clinical trials sponsored by Abbvie, Almirall, Amgen, Baxalta, Biogen, Boehringer Ingelheim, Celgene, Gebro, Janssen, JS BIOCAD, Leo-Pharma, Lilly, Merck-Serono, MSD, Mylan, Novartis, Pfizer, Regeneron, Roche, Sandoz, Samsung-Bioepis, Sanofi and UCB.
Reply to Satoshi Funada, Takashi Yoshioka, and Yan Luo’s Letter to the Editor re: Marcus J. Drake, Amanda L. Lewis, Grace J. Young, et al. Diagnostic Assessment of Lower Urinary Tract Symptoms in Men Considering Prostate Surgery: A Noninferiority Randomised Controlled Trial of Urodynamics in 26 Hospitals. Eur Urol 2020;78:701–10
Authors: Grace Young, Peter Blair, Amanda Lewis, Marcus J. Drake, J. Athene Lane
Journal: European Urology (2020)
Clinical spectrum of childhood-onset hypocomplementemic urticarial vasculitis in Oman: A retrospective multicenter study
Authors: Buthaina Hashil Al Musalhi, Ahmed Al Kamzari, Fatma Al Kindi, Safiya Al Abrawi, Ibrahim Al-Zakwani, Reem Abdwani
Journal: Journal of the American Academy of Dermatology (2020)
Multi-omics approaches identify SF3B3 and SIRT3 as candidate autophagic regulators and druggable targets in invasive breast carcinoma
Authors: Shouyue Zhang, Jin Zhang, Yang An, Xiaoxi Zeng, Ziyi Qin, Yuqian Zhao, Heng Xu, Bo Liu
Journal: Acta Pharmaceutica Sinica B (2020)

Autophagy is a critical cellular homeostatic mechanism, and its dysfunction is linked to invasive breast carcinoma (BRCA). Recently, several omics methods have been applied to explore autophagic regulators in BRCA; however, more reliable and robust approaches for identifying crucial regulators and druggable targets remain to be discovered. Thus, we report here the results of multi-omics approaches to identify potential autophagic regulators in BRCA, including gene expression (EXP), DNA methylation (MET) and copy number alterations (CNAs) from The Cancer Genome Atlas (TCGA). Newly identified candidate genes, such as SF3B3, TRAPPC10, SIRT3, MTERFD1, and FBXO5, were confirmed to be involved in the positive or negative regulation of autophagy in BRCA. SF3B3 was identified firstly as a negative autophagic regulator, and siRNA/shRNA-SF3B3 were shown to induce autophagy-associated cell death in in vitro and in vivo breast cancer models. Moreover, a novel small-molecule activator of SIRT3, 1-methylbenzylamino amiodarone, was discovered to induce autophagy in vitro and in vivo. Together, these results provide multi-omics approaches to identify some key candidate autophagic regulators, such as the negative regulator SF3B3 and positive regulator SIRT3 in BRCA, and highlight SF3B3 and SIRT3 as new druggable targets that could be used to fill the gap between autophagy and cancer drug development.
Intravenous immunoglobulin treatment for patients with severe COVID-19: a retrospective multicentre study
Authors: Jiao Liu, Yizhu Chen, Ranran Li, Zhixiong Wu, Qianghong Xu, Zhongyi Li, Djillali Annane, Huibin Feng, Sisi Huang, Jun Guo, Lidi Zhang, Xiaofei Ye, Wei Zhu, Hangxiang Du, Yong'an Liu, Tao Wang, Limin Chen, Zhenliang Wen, Jean-Louis Teboul, Dechang Chen
Journal: Clinical Microbiology and Infection (2021)
A Positive Feedback Loop of AKR1C3-Mediated Activation of NF-κB and STAT3 Facilitates Proliferation and Metastasis in Hepatocellular Carcinoma
Authors: Qingqing Zhou, Wei Tian, Zhiyuan Jiang, Tingting Huang, Chao Ge, Tengfei Liu, Fangyu Zhao, Taoyang Chen, Ying Cui, Hong Li, Ming Yao, Jinjun Li, Hua Tian
Journal: Cancer Research (2020)

AKR1C3 is an enzyme belonging to the aldo-ketoreductase family, the members of which catalyze redox transformations involved in biosynthesis, intermediary metabolism, and detoxification. AKR1C3 plays an important role in tumor progression and metastasis, however, little is known about the function and the molecular mechanism underlying the role of AKR1C3 in hepatocellular carcinoma (HCC). In this study, we report that AKR1C3 is significantly upregulated in HCC and that increased AKR1C3 is associated with poor survival. AKR1C3 positively regulated HCC cell proliferation and metastasis
Supplies of medicines, devices, and staff a serious concern as Brexit nears
Authors: Adrian O’Dowd
Journal: BMJ (2020)

The UK is facing several problems that will affect healthcare as the country nears the end of the Brexit transition period on 31 December with a perilously uncertain future, according to an independent health think tank.

The short term supply of drugs and medical devices to the UK after the transition period was “a serious concern” with high levels of uncertainty, said the Nuffield Trust’ report1 on the obstacles ahead once the UK has fully left the European Union (EU), whether or not a trade deal is agreed before then.

The research was carried out by the Nuffield Trust and academics from the universities of Oxford, Sheffield, and Michigan, and funded by the Health Foundation. It was based on policy analysis, interviews with senior officials …
Changes in Seizure Frequency and Antiepileptic Therapy during Pregnancy
Authors: Page B. Pennell, Jacqueline A. French, Ryan C. May, Elizabeth Gerard, Laura Kalayjian, Patricia Penovich, Evan Gedzelman, Jennifer Cavitt, Sean Hwang, Alison M. Pack, Maria Sam, John W. Miller, Steffanie H. Wilson, Carrie Brown, Angela K. Birnbaum, Kimford J. Meador
Journal: New England Journal of Medicine (2020)

Among women with epilepsy, studies regarding changes in seizure frequency during pregnancy have been limited by the lack of an appropriate nonpregnant comparator group to provide data on the natural course of seizure frequency in both groups.
Single-Cell Analysis of Blood-Brain Barrier Response to Pericyte Loss
Authors: Maarja A. Mäe, Liqun He, Sofia Nordling, Elisa Vazquez-Liebanas, Khayrun Nahar, Bongnam Jung, Xidan Li, Bryan C. Tan, Juat Chin Foo, Amaury Cazenave-Gassiot, Markus R. Wenk, Yvette Zarb, Barbara Lavina, Susan E. Quaggin, Marie Jeansson, Chengua Gu, David L. Silver, Michael Vanlandewijck, Eugene C. Butcher, Annika Keller, Christer Betsholtz
Journal: Circulation Research (2020)

Rationale: Pericytes are capillary mural cells playing a role in stabilizing newly formed blood vessels during development and tissue repair. Loss of pericytes has been described in several brain disorders, and genetically induced pericyte deficiency in the brain leads to increased macromolecular leakage across the blood-brain barrier (BBB). However, the molecular details of the endothelial response to pericyte deficiency remain elusive. Objective: To map the transcriptional changes in brain endothelial cells resulting from lack of pericyte contact at single-cell level and to correlate them with regional heterogeneities in BBB function and vascular phenotype. Methods and Results: We reveal transcriptional, morphological, and functional consequences of pericyte absence for brain endothelial cells using a combination of methodologies, including single-cell RNA sequencing, tracer analyses, and immunofluorescent detection of protein expression in pericyte-deficient adult Pdgfb ret/ret mice. We find that endothelial cells without pericyte contact retain a general BBB-specific gene expression profile, however, they acquire a venous-shifted molecular pattern and become transformed regarding the expression of numerous growth factors and regulatory proteins. Adult Pdgfb ret/ret brains display ongoing angiogenic sprouting without concomitant cell proliferation providing unique insights into the endothelial tip cell transcriptome. We also reveal heterogeneous modes of pericyte-deficient BBB impairment, where hotspot leakage sites display arteriolar-shifted identity and pinpoint putative BBB regulators. By testing the causal involvement of some of these using reverse genetics, we uncover a reinforcing role for angiopoietin 2 at the BBB. Conclusions: By elucidating the complexity of endothelial response to pericyte deficiency at cellular resolution, our study provides insight into the importance of brain pericytes for endothelial arterio-venous zonation, angiogenic quiescence, and a limited set of BBB functions. The BBB-reinforcing role of ANGPT2 (angiopoietin 2) is paradoxical given its wider role as TIE2 (TEK receptor tyrosine kinase) receptor antagonist and may suggest a unique and context-dependent function of ANGPT2 in the brain.
Folding Stability of Pax9 Intronic G-Quadruplex Correlates with Relative Molar Size in Eutherians
Authors: Manuel Jara-Espejo, Melissa T R Hawkins, Giovani Bressan Fogalli, Sergio Roberto Peres Line
Journal: Molecular Biology and Evolution (2020)

Abstract Eutherian dentition has been the focus of a great deal of studies in the areas of evolution, development, and genomics. The development of molar teeth is regulated by an antero-to-posterior cascade mechanism of activators and inhibitors molecules, where the relative sizes of the second (M2) and third (M3) molars are dependent of the inhibitory influence of the first molar (M1). Higher activator/inhibitor ratios will result in higher M2/M1 or M3/M1. Pax9 has been shown to play a key role in tooth development. We have previously shown that a G-quadruplex in the first intron of Pax9 can modulate the splicing efficiency. Using a sliding window approach with we analyzed the association of the folding energy (Mfe) of the Pax9 first intron with the relative molar sizes in 42 mammalian species, representing 9 orders. The Mfe of two regions located in the first intron of Pax9 were shown to be significantly associated with the M2/M1 and M3/M1 areas and mesiodistal lengths. The first region is located at the intron beginning and can fold into a stable G4 structure, whereas the second is downstream the G4 and 265 bp from intron start. Across species, the first intron of Pax9 varied in G-quadruplex structural stability. The correlations were further increased when the Mfe of the two sequences were added. Our results indicate that this region has a role in the evolution of the mammalian dental pattern by influencing the relative size of the molars.