tbuckley/cabot-search huggingface dataset:
OUP accepted manuscript
Journal: Human Reproduction Update (2020)

Endometrium is a vital multicellular tissue for progression of pregnancy. Forkhead box O1 (FoxO1) transcription factor plays an important role in the endometrium as it regulates various cellular processes with its unique expression in different cell types.This review focuses on the role of FoxO1 in endometrium with a particular emphasis on FoxO1 signaling in individual endometrial cell types during the menstrual cycle and early pregnancy.A literature search was conducted in PubMed, Web of Science and Scopus to select studies reporting the role of FoxO1 in endometrium using the keywords: FoxO1, endometrium, menstrual cycle, early pregnancy, endometrial receptivity, implantation, decidualization, angiogenesis and neoplasia. Papers published before October 2020 were selected. Drawing on advances in laboratory science and preclinical studies, we performed a narrative review of the scientific literature to provide a timely update on the roles of FoxO1 during the menstrual cycle and early pregnancy.FoxO1 is considered to be a decidualization marker in endometrial stromal cells, mainly because it regulates the transcription of decidual prolactin and insulin-like growth factor-binding protein 1 genes. Importantly, 507 of 3405 genes that are specifically regulated during decidualization of human endometrial stromal cells are expressed abnormally as a result of FOXO1 reduction. Epithelial FoxO1 is currently accepted as a novel endometrial receptivity marker for humans and mice owing to its timely and specific expression at the window of implantation. On the other hand, FOXO1 is essential in endometrial epithelial cell proliferation and differentiation to achieve endometrial homeostasis since loss of function of FOXO1 causes endometrial neoplasia. Last but not least, FoxO1 seems to act like a navigator molecule for embryo homing owing to its notably decreased nuclear expression in endometrial luminal epithelial cells, specifically at the blastocyst attachment region, which results in differentiation, entosis and apoptosis of endometrial epithelial cells during the peri-implantation period. In endothelium, FoxO1 expression coincides with the timing of increased vascular permeabilization during early pregnancy. There are limited data regarding the importance of FoxO1 upregulation in endometrial endothelial cells, therefore, it is time to investigate the role of endothelial FoxO1, which is the missing piece in the puzzle of the enigmatic endometrium. Another missing piece in the puzzle for the role of FoxO1 is on embryo development.FoxO1 is a cell-specific core transcription factor involved in efficient endometrial remodeling during the menstrual cycle and early pregnancy. A better understanding of the role of FoxO1 as a decidualization marker, as an emerging marker of endometrial receptivity, and as a therapeutic target to prevent endometrial neoplasia could help us to make sense of endometrial biology and thus to improve the outcomes of ART in the clinic.
ITGBL1 is a new immunomodulator that favors development of melanoma tumors by inhibiting natural killer cells cytotoxicity
Authors: Yann Cheli, Meri K. Tulic, Najla El Hachem, Nicolas Nottet, Arnaud Jacquel, Maeva Gesson, Thomas Strub, Karine Bille, Alexandra Picard-Gauci, Henri Montaudié, Guillaume E. Beranger, Thierry Passeron, Pierre Close, Corine Bertolotto, Robert Ballotti
Journal: Molecular Cancer (2021)

Abstract Resistances to immunotherapies remains a major hurdle towards a cure for melanoma in numerous patients. An increase in the mesenchymal phenotype and a loss of differentiation have been clearly associated with resistance to targeted therapies. Similar phenotypes have been more recently also linked to resistance to immune checkpoint therapies. We demonstrated here that the loss of MIcrophthalmia associated Transcription Factor (MITF), a pivotal player in melanocyte differentiation, favors the escape of melanoma cells from the immune system. We identified Integrin beta-like protein 1 (ITGBL1), a secreted protein, upregulated in anti-PD1 resistant patients and in MITF low melanoma cells, as the key immunomodulator. ITGBL1 inhibited immune cell cytotoxicity against melanoma cells by inhibiting NK cells cytotoxicity and counteracting beneficial effects of anti-PD1 treatment, both in vitro and in vivo . Mechanistically, MITF inhibited RUNX2, an activator of ITGBL1 transcription. Interestingly, VitaminD3, an inhibitor of RUNX2, improved melanoma cells to death by immune cells. In conclusion, our data suggest that inhibition of ITGBL1 might improve melanoma response to immunotherapies.
Beyond Antimuscarinics: A Review of Pharmacological and Interventional Options for Overactive Bladder Management in Men
Authors: Cosimo De Nunzio, Benjamin Brucker, Thomas Bschleipfer, Jean-Nicolas Cornu, Marcus J. Drake, Ferdinando Fusco, Stavros Gravas, Matthias Oelke, Benoit Peyronnet, Manuela Tutolo, Gommert van Koeveringe, Stephan Madersbacher
Journal: European Urology (2021)
Classification of lower extremity venous malformations and risk of knee involvement: A retrospective cohort study
Authors: Krystal M. Jones, Kristen C. Corey, Anna Cristina Garza-Mayers, Samantha A. Spencer, John B. Mulliken, Rush H. Chewning, Marilyn G. Liang
Journal: Journal of the American Academy of Dermatology (2021)
Incidental 68Ga–Prostate-Specific Membrane Antigen Uptake in Compression Fracture of a Vertebral Body
Authors: Selin Kesim, Kevser Oksuzoglu, Salih Ozguven, Tanju Yusuf Erdil
Journal: Clinical Nuclear Medicine (2021)

Prostate-specific membrane antigen (PSMA) is a membrane glycoprotein, which is overexpressed in prostate cancer cells. With its wide use, there is a growing number of case reports describing non-prostate cancer-related benign and malignant lesions showing increased 68Ga-PSMA uptake. We herein present the case of an 89-year-old man with prostate cancer who was referred for 68Ga-PSMA PET/CT for restaging, which revealed incidental 68Ga-PSMA uptake in compression fracture of a vertebral body. This case demonstrates that PSMA expression may occur in acute compression fractures, and it can be a potential pitfall when reporting 68Ga-PSMA PET/CT images.
Mindfulness-based programmes for mental health promotion in adults in nonclinical settings: A systematic review and meta-analysis of randomised controlled trials
Authors: Julieta Galante, Claire Friedrich, Anna F Dawson, Marta Modrego-Alarcón, Pia Gebbing, Irene Delgado-Suárez, Radhika Gupta, Lydia Dean, Tim Dalgleish, Ian R White, Peter B Jones
Journal: PLoS Medicine (2021)

There is an urgent need for mental health promotion in nonclinical settings. Mindfulness-based programmes (MBPs) are being widely implemented to reduce stress, but a comprehensive evidence synthesis is lacking. We reviewed trials to assess whether MBPs promote mental health relative to no intervention or comparator interventions.
Tumor Mutational Burden Is Polygenic and Genetically Associated with Complex Traits and Diseases
Authors: Xiwei Sun, Angli Xue, Ting Qi, Dan Chen, Dandan Shi, Yang Wu, Zhili Zheng, Jian Zeng, Jian Yang
Journal: Cancer Research (2021)

Abstract Tumor mutational burden (TMB) is an emerging biomarker of response to immunotherapy in solid tumors. However, the extent to which variation in TMB between patients is attributable to germline genetic variation remains elusive. Here, using 7,004 unrelated patients of European descent across 33 cancer types from The Cancer Genome Atlas, we show that pan-cancer TMB is polygenic with approximately 13% of its variation explained by approximately 1.1 million common variants altogether. We identify germline variants that affect TMB in stomach adenocarcinoma through altering the expression levels of BAG5 and KLC1. Further analyses provide evidence that TMB is genetically associated with complex traits and diseases, such as smoking, rheumatoid arthritis, height, and cancers, and some of the associations are likely causal. Overall, these results provide new insights into the genetic basis of somatic mutations in tumors and may inform future efforts to use genetic variants to stratify patients for immunotherapy. Significance: This study provides evidence for a polygenic architecture of tumor mutational burden and opens an avenue for the use of whole-genome germline genetic variations to stratify patients with cancer for immunotherapy.
NICE’s approach to measuring value
Authors: Felix Greaves, Meindert Boysen
Journal: BMJ (2021)

Appleby asks whether covid-19 vaccines would be considered cost effective using the National Institute for Health and Care Excellence (NICE) approach to measuring value—and questions whether NICE’s methods are appropriate.1

The pandemic has highlighted fundamental questions about what we choose to value in society, including how to balance health impacts with wider societal and economic effects. Appleby is correct that we don’t consider the benefit and costs of vaccines at NICE. We see this momentous event as an …
What can experimental studies of bias tell us about real-world group disparities?
Authors: Joseph Cesario
Journal: Behavioral and Brain Sciences (2021)

This article questions the widespread use of experimental social psychology to understand real-world group disparities. Standard experimental practice is to design studies in which participants make judgments of targets who vary only on the social categories to which they belong. This is typically done under simplified decision landscapes and with untrained decision-makers. For example, to understand racial disparities in police shootings, researchers show pictures of armed and unarmed Black and White men to undergraduates and have them press "shoot" and "don't shoot" buttons. Having demonstrated categorical bias under these conditions, researchers then use such findings to claim that real-world disparities are also due to decision-maker bias. I describe three flaws inherent in this approach, flaws which undermine any direct contribution of experimental studies to explaining group disparities. First, the decision landscapes used in experimental studies lack crucial components present in actual decisions (missing information flaw). Second, categorical effects in experimental studies are not interpreted in light of other effects on outcomes, including behavioral differences across groups (missing forces flaw). Third, there is no systematic testing of whether the contingencies required to produce experimental effects are present in real-world decisions (missing contingencies flaw). I apply this analysis to three research topics to illustrate the scope of the problem. I discuss how this research tradition has skewed our understanding of the human mind within and beyond the discipline and how results from experimental studies of bias are generally misunderstood. I conclude by arguing that the current research tradition should be abandoned.
Melflufen: A Next-Generation Nitrogen Mustard
Authors: Sarah A. Holstein, Jens Hillengass, Philip L. McCarthy
Journal: Journal of Clinical Oncology (2021)

Article Tools UNDERSTANDING THE PATHWAY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES Melflufen and Dexamethasone in Heavily Pretreated Relapsed and Refractory Multiple Myeloma. December 09, 2020 ARTICLE CITATION DOI: 10.1200/JCO.20.03326 Journal of Clinical Oncology - published online before print January 13, 2021 PMID: 33439689 Melflufen: A Next-Generation Nitrogen Mustard Sarah A. Holstein , MD, PhD1xSarah A. HolsteinSearch for articles by this author; Jens Hillengass , MD2xJens HillengassSearch for articles by this author; and Philip L. McCarthy, MD2xPhilip L. McCarthySearch for articles by this author Show More 1Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE2Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY https://doi.org/10.1200/JCO.20.03326 First Page Full Text PDF Figures and Tables © 2021 by American Society of Clinical OncologyAUTHOR CONTRIBUTIONSConception and Design: All authorsCollection and assembly of data: Sarah A. Holstein, Philip L. McCarthyData analysis and interpretation: All authorsManuscript writing: All authorsFinal approval of manuscript: All authorsAccountable for all aspects of the work: All authorsAUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTERESTMelflufen: A Next-Generation Nitrogen MustardThe following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center.Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).Sarah A. HolsteinConsulting or Advisory Role: Celgene, Adaptive Biotechnologies, GlaxoSmithKline, Sorrento Therapeutics, Genentech, Takeda, Oncopeptides, SanofiResearch Funding: OncopeptidesJens HillengassEmployment: Roswell Park Cancer InstituteHonoraria: Amgen, Janssen Biotech, Takeda, Adaptive Biotechnologies, OncoTracker, GlaxoSmithKline, Bristol-Myers Squibb, SanofiResearch Funding: CelgeneTravel, Accommodations, Expenses: Amgen, Janssen Biotech, Rocket Medical, Celgene, Takeda, Adaptive Biotechnologies, Bristol-Myers SquibbPhilip L. McCarthyHonoraria: Celgene, Karyopharm Therapeutics, Bristol-Myers Squibb, Sanofi, Janssen, The Binding SiteConsulting or Advisory Role: Celgene, Bristol-Myers Squibb, Karyopharm Therapeutics, Sanofi, Janssen, The Binding Site, Magenta Therapeutics, Bluebird BioResearch Funding: CelgeneNo other potential conflicts of interest were reported. Companion Melflufen and Dexamethasone in Heavily Pretreated Relapsed and Refractory Multiple Myeloma
Rehabilitation for adults with complex psychosis: summary of NICE guidance
Authors: Helen Killaspy, Gillian Baird, Nathan Bromham, Angela Bennett
Journal: BMJ (2021)

### What you need to know

Providing rehabilitation for people with complex psychosis enables them to achieve and sustain a rewarding life in the community.123 This article summarises the first guideline from the National Institute for Health and Care Excellence (NICE) on mental health rehabilitation for adults with complex psychosis.4 It describes how to identify people who should be offered rehabilitation, what rehabilitation services should be provided within the local mental health service, and the treatment programmes that these services should offer.

NICE recommendations are based on systematic reviews of best available evidence and explicit consideration of cost effectiveness. When minimal evidence is available, recommendations are based on the guideline development group (GC)’s experience and opinion of what constitutes good practice. Evidence levels for the recommendations are given in italic in square brackets.

### What is rehabilitation for people with complex psychosis?

Approximately 20% of people with schizophrenia and other psychoses have particularly complex problems that impair functioning and lead to recurrent admission to hospital.5 These problems include severe, treatment-resistant symptoms and cognitive impairments that affect motivation, organisational and social skills, as well as additional mental, neurodevelopmental, and physical health conditions. People in this group require longer term, specialist rehabilitation services to optimise their response to treatment and enable them to gain the skills and confidence to live as independently as possible and …
Circular RNA in pancreatic cancer: a novel avenue for the roles of diagnosis and treatment
Authors: Zeyin Rong, Jin Xu, Si Shi, Zhen Tan, Qingcai Meng, Jie Hua, Jiang Liu, Bo Zhang, Wei Wang, Xianjun Yu, Chen Liang
Journal: Theranostics (2021)

Pancreatic cancer (PC), an important cause of cancer-related deaths worldwide, is one of the most malignant cancers characterized by a dismal prognosis. Circular RNAs (circRNAs), a class of endogenous ncRNAs with unique covalently closed loops, have attracted great attention in regard to various diseases, especially cancers. Compelling studies have suggested that circRNAs are aberrantly expressed in different cancer tissues and cell types, including PC. More specifically, circRNAs can modify the proliferation, progression, tumorigenesis and chemosensitivity of PC, and some circRNAs could serve as biomarkers for diagnosis and prognosis. Herein, we summarize what is currently known to be related to the biogenesis, functions and potential roles of human circRNAs in PC and their application prospects for PC clinical treatments.
What have we learnt so far from COVID-19?
Authors: Peter C. Doherty
Journal: Nature reviews. Immunology (2021)

While COVID-19 shows us the enormous power of modern molecular medicine, it also reminds us of the basic contradictions and limitations of the human condition. As it is highly likely we will experience further such events through the twenty-first century, we should regard COVID-19 as a training run for something that could be much worse, and organize our governance, global interactions, institutions and practices accordingly. In this World View article, eminent immunologist Peter Doherty suggests that we should consider the COVID-19 crisis as a training run for future, potentially worse pandemics and organize accordingly.
Targeting CDK7 suppresses super enhancer-linked inflammatory genes and alleviates CAR T cell-induced cytokine release syndrome
Authors: Ye Wei, Chong Li, Huifang Bian, Wei Qian, Kairui Jin, Tingting Xu, Xiaomao Guo, Xueguan Lu, Fengtao Su
Journal: Molecular Cancer (2021)

Abstract Background Cytokine release syndrome (CRS) is a systemic inflammatory response characterized by the overexpression of inflammatory genes. Controlling CRS is essential for improving the therapeutic effects of chimeric antigen receptor (CAR) engineered T cells. However, current treatment options are limited given the complexity of cytokine interactions so it is important to seek a mild strategy with broad-spectrum inhibition to overcome this challenge. Methods Using THZ1, a covalent inhibitor of cyclin-dependent kinase 7 (CDK7), we demonstrated the transcriptional suppression of inflammatory genes in activated macrophages. RNA sequencing and ChIP sequencing were conducted to identify the key target genes of the inflammatory response. Pathogen- and CAR T cell-induced CRS models were also established to assess the efficacy and safety of targeting CDK7. Results CDK7 blockade attenuated cytokine release, mitigated hyperinflammatory states and rescued mice from lethal CRS. Targeting CDK7 preferentially suppressed a set of inflammatory genes, of which STAT1 and IL1 were the key targets associated with super enhancers. Furthermore, we confirmed the potent efficacy of THZ1 in alleviating the CRS induced by CAR T cell infusion without causing tissue injury or impairing antitumor effects. Conclusions Our work indicates the CDK7-dependent transcription addiction of inflammatory genes. Targeting CDK7 is a promising strategy for treating CRS by inhibiting multiple cytokines.
Detection of group B streptococcus colonisation in pregnant women: Comparison of two different culture methods and study of antimicrobial resistance patterns
Authors: Clara Carreras-Abad, Ka-Ning To, Laxmee Ramkhelawon, Tim Planche, Irene Monahan, Abdelmajid Djennad, Vicki Chalker, Paul T Heath, Kirsty Le Doare
Journal: Journal of Infection (2021)
The integration of immune checkpoint inhibitors with VEGF targeted agents in advanced gastric and gastroesophageal adenocarcinoma: a review on the rationale and results of early phase trials
Authors: Anwaar Saeed, Robin Park, Weijing Sun
Journal: Journal of Hematology & Oncology (2021)

Abstract Several targeted therapies have shown efficacy in patients with advanced gastric cancer (GC) and gastroesophageal junction adenocarcinoma (GEJC), including anti-angiogenic agents and immune checkpoint inhibitors. Ramucirumab, an anti-VEGFR2 antibody, has shown efficacy in GC, but the benefits are limited, in part due to MET-mediated resistance. Other VEGF targeted agents like VEGF tyrosine kinase inhibitors (TKIs) with broad multi-kinase inhibitory spectrum like regorafenib and cabozantinib have also shown modest single agent activity in early phase trials. For immune checkpoint inhibitors, pembrolizumab (anti-PD-1) monotherapy confers survival advantage as 3rd line therapy for the PD-L1 expressing GC and GEJC population and has been approved for use in this setting. Extensive tumor microenvironment immune modulatory effects from antiangiogenic agents have been demonstrated from preclinical data which support the clinical study rationale of dual blockade of VEGF and immune checkpoint. In addition, FDA has approved combinations of anti-VEGF/VEGFR with anti-PD-1/PD-L1 agents in hepatocellular carcinoma and renal cell carcinoma. Promising clinical activity has been demonstrated in patients with refractory GC/GEJC when treated with dual blockade combination with antiangiogenic agents and immune checkpoint inhibitors like PD-1/PD-L1 inhibitors in several phase I/II trials. This review highlights the trials investigating these novel combinations as well as their preclinical rationale.
Rac1 and Connective Tissue Growth Factor: The Missing Link Between Atrial Remodeling and the Pathogenesis of Atrial Fibrillation?**Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: James K. Liao
Journal: Journal of the American College of Cardiology (2010)