tbuckley/cabot-search huggingface dataset:
Pretreatment<sup> 18</sup>F-FDG uptake heterogeneity predicts response to pyrotinib in patients with metastatic HER2-positive breast cancer.
Authors: Cc Gong, Cheng Liu, Zhonghua Tao, Jian Zhang, Leiping Wang, Jun Cao, Yannan Zhao, Yi Li, Yizhao Xie, Biyun Wang, Zhongyi Yang, Xichun Hu
Journal: Journal of Clinical Oncology (2021)

e15026 Background: Heterogeneity of 18 F-fluorodeoxyglucose (FDG) uptake is a promising marker for predicting response to treatment. This study aimed to evaluate the ability of pretreatment positron emission tomography/computed tomography (PET/CT) 18 F-FDG-based heterogeneity to predict the response to pyrotinib in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC). Methods: Patients with MBC in the Fudan University Shanghai Cancer Center who underwent whole-body 18 F-FDG PET/CT before the initiation of pyrotinib was included. The intertumoral and intratumoral heterogeneity indexes (HI-inter and HI-intra, respectively), maximum standardized uptake value (SUVmax), total lesion glycolysis (TLG), and metabolic tumor volume (MTV) on the baseline PET/CT were assessed. Progression-free survival (PFS) was estimated by the Kaplan-Meier method and compared by log-rank test. Time-dependent receiver operating characteristic (ROC) curve analysis was performed, and the predictive accuracies of all markers were evaluated by plotting the cumulative area under the ROC curve (AUC) over time. Results: A total of 22 patients were included in this study. The median PFS of patients with a high HI-intra (&gt; 1.9) was 6.6 months, whereas that of patients with a low HI-intra was 13.4 months (p = 0.044). The HI-inter was able to discriminate patients as well as the coefficient of variance. Univariate analysis showed that patients with a higher HI-inter tended to have worse PFS (10.6 months vs. 13.4 months, p = 0.067). Higher SUVmax and TLG were also associated with worse PFS. ROC curve analysis confirmed the predictive value of the HI-inter and HI-intra. TLG had the highest accuracy in predicting PFS (AUC = 0.87), followed by HI-inter (AUC = 0.86), SUVmax (AUC = 0.85), HI-intra (AUC = 0.80), mean standardized uptake value (AUC = 0.63), and MTV (AUC = 0.60). Conclusions: Intratumoral and intertumoral heterogeneities in metastatic lesions on pretreatment 18 F-FDG PET/CT could predict response to pyrotinib treatment in patients with HER2-positive breast cancer, which could provide information to guide treatment decisions.
ExOrthist: a tool to infer exon orthologies at any evolutionary distance
Authors: Yamile Márquez, Federica Mantica, Luca Cozzuto, Demian Burguera, Antonio Hermoso-Pulido, Julia Ponomarenko, Scott W. Roy, Manuel Irimia
Journal: Genome biology (2021)

Abstract Several bioinformatic tools have been developed for genome-wide identification of orthologous and paralogous genes. However, no corresponding tool allows the detection of exon homology relationships. Here, we present ExOrthist , a fully reproducible Nextflow -based software enabling inference of exon homologs and orthogroups, visualization of evolution of exon-intron structures, and assessment of conservation of alternative splicing patterns. ExOrthist evaluates exon sequence conservation and considers the surrounding exon-intron context to derive genome-wide multi-species exon homologies at any evolutionary distance. We demonstrate its use in different evolutionary scenarios: whole genome duplication in frogs and convergence of Nova -regulated splicing networks ( https://github.com/biocorecrg/ExOrthist ).
Helminth–virus interactions: determinants of coinfection outcomes
Authors: Pritesh Desai, Michael S. Diamond, Larissa B. Thackray
Journal: Gut Microbes (2021)

Viral infections are often studied in model mammalian organisms under specific pathogen-free conditions. However, in nature, coinfections are common, and infection with one organism can alter host susceptibility to infection with another. Helminth parasites share a long coevolutionary history with mammalian hosts and have shaped host physiology, metabolism, immunity, and the composition of the microbiome. Published studies suggest that helminth infection can either be beneficial or detrimental during viral infection. Here, we discuss coinfection studies in mouse models and use them to define key determinants that impact outcomes, including the type of antiviral immunity, the tissue tropism of both the helminth and the virus, and the timing of viral infection in relation to the helminth lifecycle. We also explore the current mechanistic understanding of how helminth-virus coinfection impacts host immunity and viral pathogenesis. While much attention has been placed on the impact of the gut bacterial microbiome on immunity to infection, we suggest that enteric helminths, as a part of the eukaryotic macrobiome, also represent an important modulator of disease pathogenesis and severity following virus infection.
Transcriptomic and Network Signatures of Cryptic Fusion CBFA2T3-GLIS2 in Pediatric AML Reveals Clinical Considerations and Implications
Authors: Jenny L. Smith, Rhonda E. Ries, Heather Louise Schuback, Lisa E. Brodersen, Michael R. Loken, Hamid Bolouri, Soheil Meshinchi
Journal: Blood (2017)
Development of a furosemide-containing expandable system for gastric retention
Authors: Marco Neumann, Claudia Heimhardt, Knut Seidlitz, Mirko Koziolek, Felix Schneider, Christiane Schiller, Ulrike Hanke, Maria Anschütz, Christian Knopke, Frank Donath, Rudy Thoma, Christian Brätter, Barbara Schug, Hanshermann Franke, Werner Weitschies
Journal: Journal of Controlled Release (2021)
P-97 Updated results of HGCSG1603: A phase 2 trial of ramucirumab plus irinotecan combination therapy as second-line treatment for patients with advanced gastric cancer
Authors: M. Nakamura, Y. Kawamoto, S. Yuki, K. Sawada, O. Muto, S. Sogabe, Y. Shindo, A. Ishiguro, A. Sato, Y. Tsuji, M. Dazai, H. Okuda, T. Sasaki, K. Harada, H. Nakatsumi, K. Iuchi, Y. Sakata, Y. Komatsu
Journal: Annals of Oncology (2021)
Graphene oxide-functionalized nanocomposites promote osteogenesis of human mesenchymal stem cells via enhancement of BMP-SMAD1/5 signaling pathway
Authors: Zhong Li, Shiqi Xiang, Zixuan Lin, Eileen N. Li, Haruyo Yagi, Guorui Cao, Lauren Yocum, La Li, Tingjun Hao, Katherine K. Bruce, Madalyn R. Fritch, Huanlong Hu, Bing Wang, Peter G. Alexander, Khiam Aik Khor, Rocky S. Tuan, Hang Lin
Journal: Biomaterials (2021)
25665 Efficacy and safety of mirikizumab in psoriasis: 52-week results from the OASIS-1 randomized controlled trial
Authors: Andrew Blauvelt, Alexa B. Kimball, Matthias Augustin, Yukari Okubo, Michael Witte, Claudia Rodriguez Capriles, Angelina Sontag, Vipin Arora, Olawale Osuntokun, Bruce Strober
Journal: Journal of the American Academy of Dermatology (2021)
Deep Learning for Automatic Calcium Scoring in Population-Based Cardiovascular Screening
Authors: Marleen Vonder, Sunyi Zheng, Monique D. Dorrius, Carlijn M. van der Aalst, Harry J. de Koning, Jaeyoun Yi, Donghoon Yu, Jan Willem C. Gratama, Dirkjan Kuijpers, Matthijs Oudkerk
Journal: JACC. Cardiovascular imaging (2021)
Incidence of myelodysplastic syndromes (tMDS) and acute myeloid leukemia (tAML) in patients with low-grade non-Hodgkin's lymphoma (LG-NHL) treated with Bexxar (TM).
Authors: JM Bennett, AD Zelenetz, OW Press, JM Vose, JA Radford, SJ Knox, M Wilkinson, RS Schwartz, Kaminski, R Capizzi
Journal: Blood (2001)
Covid-19: Which countries are doing well on test and trace—and how can we tell?
Authors: Chris Stokel-Walker
Journal: BMJ (2021)

Covid-19: Which countries are doing well on test and trace-and how can we tell?With the UK's test and trace scheme much maligned, Chris Stokel-Walker asks which countries have done better, and how we can measure "success"? Chris Stokel-Walker freelance journalistResearch by Imperial College London suggests effective test, trace, and isolate systems could reduce the reproductive rate of SARS-CoV-2 by 26%. 1 Yet different countries have had wildly different levels of success with their systems.Measuring "success," however, is hard.Systematic reviews of test and trace systems worldwide often struggle to provide a definitive answer. 2 "It all depends on the outcome measure," says Jay Patel,
P-42 Reduced-dose of doublet chemotherapy combined with anti-EGFR antibodies as treatment option in vulnerable older patients with metastatic colorectal cancer: A retrospective cohort study
Authors: G. Rosati, D. Corsi, A. Avallone, S. Brugnatelli, E. Dell'Aquila, N. Pella, A. Cappetta, G. Cicero, C. Carlomagno, A. Colombo, S. Rapisardi, C. Pinto, M. Cantore, D. Germano, G. Reggiardo
Journal: Annals of Oncology (2021)
Tocilizumab for coronavirus disease 2019 in pregnancy and lactation: a narrative review
Authors: Sarah C.J. Jorgensen, Stephen E. Lapinsky
Journal: Clinical Microbiology and Infection (2021)

BackgroundTocilizumab is a monoclonal antibody that interrupts interleukin-6 signalling, reducing downstream effects on inflammation and the innate immune response. It was shown to reduce mortality in patients with severe or critical coronavirus disease 2019 (COVID-19). Pregnant and breastfeeding people were largely excluded from clinical trials and hence, the extent to which results can be applied to these populations is not clear.ObjectivesTo synthesize published data on tocilizumab in pregnancy and lactation, highlight important knowledge gaps, and help inform clinical decision-making about tocilizumab's use in these populations with COVID-19.SourcesPubMed was searched for studies evaluating tocilizumab in pregnancy and lactation for COVID-19 and other indications. Literature on pharmacokinetics and reproductive/fetal safety of monoclonal antibodies in general was also sought. The US Food and Drug Administration and the European Medicines Agency guidance for the industry and regulatory approval documents were reviewed.ContentPublished data on tocilizumab in pregnancy include 610 cases (n = 20 with COVID-19) together with seven mother–infant breastfeeding pairs. Higher rates of spontaneous abortion and premature birth have been reported compared with the general population, but multiple confounding variables limit interpretation. There is little data on tocilizumab exposure in the second and third trimesters when transplacental transport is highest. The effects of tocilizumab on the developing immune system are unclear. Pregnant patients with COVID-19 who received tocilizumab were often critically ill and corticosteroid use was uncommon. Neonatal follow up was limited. Tocilizumab appears to be compatible with breastfeeding.ImplicationsAlthough the available data do not raise serious safety signals, they have significant limitations and are not sufficient to delineate the complete spectrum of potential adverse outcomes that may be associated with tocilizumab exposure during pregnancy and lactation. Diligent follow up and documentation of pregnancy outcomes will be important moving forward. A more effective regulatory framework to ensure equitable inclusion of pregnant people in research is clearly needed.
Practicable Applications of Aggregation‐Induced Emission with Biomedical Perspective
Authors: Yuqing Wang, Bozhang Xia, Qianqian Huang, Ting Luo, Yuanyuan Zhang, Peter Timashev, Weisheng Guo, Fangzhou Li, Xing‐Jie Liang
Journal: Advanced Healthcare Materials (2021)

Abstract Considerable efforts have been made into developing aggregation‐induced emission fluorogens (AIEgens)‐containing nano‐therapeutic systems due to the excellent properties of AIEgens. Compared to other fluorescent molecules, AIEgens have advantages including low background, high signal‐to‐noise ratio, good sensitivity, and resistance to photobleaching, in addition to being exempt from concentration quenching or aggregation‐caused quenching effects. The present review outlines the major developments in the biomedical applications of AIEgens‐containing systems. From a literature survey, the recent AIE works are reviewed and the reasons why AIEgens are chosen in various biomedical applications are highlighted. The research activities on AIEgens‐containing systems are increasing rapidly, therefore, the present review is timely.
Cardiovascular comorbidities, inflammation, and cerebral small vessel disease
Authors: Lowri E Evans, Jade L Taylor, Craig J Smith, Harry A T Pritchard, Adam S Greenstein, Stuart M Allan
Journal: Cardiovascular Research (2021)

Abstract Cerebral small vessel disease (cSVD) is the most common cause of vascular cognitive impairment and affects all levels of the brain’s vasculature. Features include diverse structural and functional changes affecting small arteries and capillaries that lead to a decline in cerebral perfusion. Due to an ageing population, incidence of cSVD is continually rising. Despite its prevalence and its ability to cause multiple debilitating illnesses, such as stroke and dementia, there are currently no therapeutic strategies for the treatment of cSVD. In the healthy brain, interactions between neuronal, vascular, and inflammatory cells are required for normal functioning. When these interactions are disturbed, chronic pathological inflammation can ensue. The interplay between cSVD and inflammation has attracted much recent interest, and this review discusses chronic cardiovascular diseases, particularly hypertension, and explores how the associated inflammation may impact on the structure and function of the small arteries of the brain in cSVD. Molecular approaches in animal studies are linked to clinical outcomes in patients, and novel hypotheses regarding inflammation and cSVD are proposed that will hopefully stimulate further discussion and study in this important area.
27611 Fixed-combination halobetasol propionate 0.01%/tazarotene 0.045% (HP/TAZ) lotion for the treatment of plaque psoriasis in patients with 3-5% body surface area (BSA) and poor quality of life (QoL)
Authors: Linda Stein Gold, Edward Lain, Jerry Bagel, Abby Jacobson
Journal: Journal of the American Academy of Dermatology (2021)
Tissue-specific Tregs in cancer metastasis: opportunities for precision immunotherapy
Authors: Laura A. Huppert, Michael D. Green, Luke Kim, Christine Chow, Yan Leyfman, Adil I. Daud, James C. Lee
Journal: Cellular and Molecular Immunology (2021)

Abstract Decades of advancements in immuno-oncology have enabled the development of current immunotherapies, which provide long-term treatment responses in certain metastatic cancer patients. However, cures remain infrequent, and most patients ultimately succumb to treatment-refractory metastatic disease. Recent insights suggest that tumors at certain organ sites exhibit distinctive response patterns to immunotherapy and can even reduce antitumor immunity within anatomically distant tumors, suggesting the activation of tissue-specific immune tolerogenic mechanisms in some cases of therapy resistance. Specialized immune cells known as regulatory T cells (Tregs) are present within all tissues in the body and coordinate the suppression of excessive immune activation to curb autoimmunity and maintain immune homeostasis. Despite the high volume of research on Tregs, the findings have failed to reconcile tissue-specific Treg functions in organs, such as tolerance, tissue repair, and regeneration, with their suppression of local and systemic tumor immunity in the context of immunotherapy resistance. To improve the understanding of how the tissue-specific functions of Tregs impact cancer immunotherapy, we review the specialized role of Tregs in clinically common and challenging organ sites of cancer metastasis, highlight research that describes Treg impacts on tissue-specific and systemic immune regulation in the context of immunotherapy, and summarize ongoing work reporting clinically feasible strategies that combine the specific targeting of Tregs with systemic cancer immunotherapy. Improved knowledge of Tregs in the framework of their tissue-specific biology and clinical sites of organ metastasis will enable more precise targeting of immunotherapy and have profound implications for treating patients with metastatic cancer.
In vivo gene editing works in humans: Results of a phase 1 clinical trial for TTR amyloidosis
Authors: Ana Rita Batista, Terence R. Flotte
Journal: Molecular Therapy (2021)

The recent report by Gillmore et al. 1 Gillmore J.D. Gane E. Taubel J. Kao J. Fontana M. Maitland M.L. Seitzer J. O’Connell D. Walsh K.R. Wood K. et al. CRISPR-Cas9 In Vivo Gene Editing for Transthyretin Amyloidosis. N. Engl. J. Med. 2021; 385: 493-502 Crossref PubMed Scopus (207) Google Scholar describes the outcome of a small phase 1 clinical study of in vivo gene editing in six patients with hereditary transthyretin (hATTR) amyloidosis using a lipid nanoparticle (LNP) encapsulating mRNA for Cas9 combined with a single short guide RNA (sgRNA) targeting the transthyretin (TTR) gene. Intravenous (i.v.) administration of this agent (NTLA-2001) was safe and resulted in substantial reductions in serum TTR protein concentrations (47% to 96%) mediated by introduction of double-strand breaks (DSBs) into the TTR gene in hepatocytes, causing indels in TTR that disrupted its expression in a dose-dependent manner. This paper is the first report of clinical safety and molecular efficacy of i.v. delivery of CRISPR-Cas9 to treat a genetic disorder. Given the broad range of genetic disorders involving the liver, these findings could set the stage for a number of future CRISPR-based clinical products. This study only involved gene disruption, rather than gene repair, and only directly addresses the feasibility of treating conditions in which knockdown of expression is the primary goal. Therapy for disorders whose treatment requires the additional editing components needed for homology-directed repair (HDR) could potentially be less efficient. Further studies are needed to determine whether such disorders could be treated using this same platform technology.
新規発症非弁膜症性心房細動の予測因子としてのスペックルトラッキング心エコー検査における非侵襲性肺毛細管楔入圧評価-4年間前向き研究(NIPAF研究)
Authors: Kawasaki Masanori, Tanaka Ryuhei, Yoshida Akihiro, Nagaya Maki, Minatoguchi Shingo, Yoshizane Takashi, Watanabe Takatomo, Kanamori Hiromitsu, Ono Koji, Hirose Takeshi, Noda Toshiyuki, Watanabe Sachiro
Journal: Circulation (2018)
27424 Infections in adults with moderate-to-severe atopic dermatitis treated with dupilumab: long-term data from an open-label extension (OLE) study
Authors: Andrew Blauvelt, Andreas Wollenberg, Lawrence Eichenfield, Zhen Chen, Debra Sierka, Faisal A. Khokhar, Brad Shumel, Sonya L. Cyr
Journal: Journal of the American Academy of Dermatology (2021)
P0520 - Tight undergarment and tucking impair semen quality: A prospective cohort study in trans women: EAU21 Virtual Congress
Authors: I. de Nie, J. Asseler, A. Meißner, I. Voorn-De Warem, H. Kostelijk, M. Den Heijer, J. Huirne, N. Van Mello
Journal: European Urology (2021)
27833 Impact of facial atrophic acne scars on quality of life (QoL) in female adults: A multicountry population-based survey
Authors: Brigitte Dréno, Stefan Beissert, Fran E. Cook-Bolden, Rajeev Chavda, Julie C. Harper, Adelaide A. Hebert, Edward Lain, Alison Layton, Marco Rocha, Jonathan S. Weiss, Jerry K.L. Tan
Journal: Journal of the American Academy of Dermatology (2021)
Reply
Authors: Cynthia Wat, Edward Gane, Man‐Fung Yuen, Vedran Pavlovic, Henrik Mueller, Ben‐Fillippo Krippendorff, Joseph F. Grippo, Soren Ottosen
Journal: Hepatology (2021)

Firstly, Dr Vaillant proposes RO7062931 should have exhibited greater HBsAg reductions, given the efficient RO7062931 liver uptake, rapid turnover of HBsAg, and rapid protein reductions observed with GalNAc-ASOs in other therapeutic indications. We find this reasoning unsatisfactory, primarily as there should be no expectations of similar potency for GalNAc-ASOs targeting different mRNA species.
Persistent RNA virus infection is short-lived at the single-cell level but leaves transcriptomic footprints
Authors: Peter Reuther, Katrin Martin, Mario Kreutzfeldt, Matias Ciancaglini, Florian Geier, Diego Calabrese, Doron Merkler, Daniel D. Pinschewer
Journal: The Journal of Experimental Medicine (2021)

Several RNA viruses can establish life-long persistent infection in mammalian hosts, but the fate of individual virus-infected cells remains undefined. Here we used Cre recombinase–encoding lymphocytic choriomeningitis virus to establish persistent infection in fluorescent cell fate reporter mice. Virus-infected hepatocytes underwent spontaneous noncytolytic viral clearance independently of type I or type II interferon signaling or adaptive immunity. Viral clearance was accompanied by persistent transcriptomic footprints related to proliferation and extracellular matrix remodeling, immune responses, and metabolism. Substantial overlap with persistent epigenetic alterations in HCV-cured patients suggested a universal RNA virus-induced transcriptomic footprint. Cell-intrinsic clearance occurred in cell culture, too, with sequential infection, reinfection cycles separated by a period of relative refractoriness to infection. Our study reveals that systemic persistence of a prototypic noncytolytic RNA virus depends on continuous spread and reinfection. Yet undefined cell-intrinsic mechanisms prevent viral persistence at the single-cell level but give way to profound transcriptomic alterations in virus-cleared cells.
Differential Patterns of Delayed Emotion Circuit Maturation in Abused Girls With and Without Internalizing Psychopathology
Authors: Taylor J. Keding, Sara A. Heyn, Justin D. Russell, Xiaojin Zhu, Josh Cisler, Katie A. McLaughlin, Ryan J. Herringa
Journal: American Journal of Psychiatry (2021)

Childhood abuse represents one of the most potent risk factors for developing psychopathology, especially in females. Evidence suggests that exposure to early-life adversity may be related to advanced maturation of emotion processing neural circuits. However, it remains unknown whether abuse is related to early circuit maturation and whether maturation patterns depend on the presence of psychopathology.
Insertion of atypical glycans into the tumor antigen-binding site identifies DLBCLs with distinct origin and behavior
Authors: Giorgia Chiodin, Joel D. Allen, Dean J. Bryant, Philip Rock, Enrica A. Martino, Beatriz Valle-Argos, Patrick J. Duriez, Yasunori Watanabe, Isla Henderson, James S. Blachly, Katy J. McCann, Jonathan C. Strefford, Graham Packham, Teunis B. H. Geijtenbeek, Carl G. Figdor, George W. Wright, Louis M. Staudt, Richard Burack, Thomas A. Bowden, Max Crispin, Freda K. Stevenson, Francesco Forconi
Journal: Blood (2021)
28423 Treatment of cutaneous lesions in patient with blue rubber bleb nevus with diode laser
Authors: Vien The Tran, Phung Kim Thi Ngo, Minh Van Hoang, Anh Quynh Ngoc Phan, Tri Cao Le, Giang Huong Tran, Quy Thanh To
Journal: Journal of the American Academy of Dermatology (2021)
A Personalized Prediction Model to Risk Stratify Patients with Acute Myeloid Leukemia (AML)
Authors: Aziz Nazha, Sudipto Mukherjee, Karam Al-Issa, Ahed Makhoul, Vera Adema, Cassandra M. Hirsch, Anjali S. Advani, Aaron T. Gerds, Matt Kalaycio, Hetty E. Carraway, Jaroslaw P. Maciejewski, Mikkael A. Sekeres
Journal: Blood (2017)