tbuckley/cabot-search huggingface dataset:
Bioengineered miR-124-3p prodrug selectively alters the proteome of human carcinoma cells to control multiple cellular components and lung metastasis in vivo
Authors: Linglong Deng, Hannah Petrek, Mei-Juan Tu, Neelu Batra, Ai-Xi Yu, Ai-Ming Yu
Journal: Acta Pharmaceutica Sinica B (2021)

With the understanding of microRNA (miRNA or miR) functions in tumor initiation, progression, and metastasis, efforts are underway to develop new miRNA-based therapies. Very recently, we demonstrated effectiveness of a novel humanized bioengineered miR-124-3p prodrug in controlling spontaneous lung metastasis in mouse models. This study was to investigate the molecular and cellular mechanisms by which miR-124-3p controls tumor metastasis. Proteomics study identified a set of proteins selectively and significantly downregulated by bioengineered miR-124-3p in A549 cells, which were assembled into multiple cellular components critical for metastatic potential. Among them, plectin (PLEC) was verified as a new direct target for miR-124-3p that links cytoskeleton components and junctions. In miR-124-3p-treated lung cancer and osteosarcoma cells, protein levels of vimentin, talin 1 (TLN1), integrin beta-1 (ITGB1), IQ motif containing GTPase activating protein 1 (IQGAP1), cadherin 2 or N-cadherin (CDH2), and junctional adhesion molecule A (F11R or JAMA or JAM1) decreased, causing remodeling of cytoskeletons and disruption of cell-cell junctions. Furthermore, miR-124-3p sharply suppressed the formation of focal adhesion plaques, leading to reduced cell adhesion capacity. Additionally, efficacy and safety of biologic miR-124-3p therapy was established in an aggressive experimental metastasis mouse model in vivo. These results connect miR-124-3p-PLEC signaling to other elements in the control of cytoskeleton, cell junctions, and adhesion essential for cancer cell invasion and extravasation towards metastasis, and support the promise of miR-124 therapy.
NCCN Guidelines® Insights: Uterine Neoplasms, Version 3.2021
Authors: Nadeem R. Abu-Rustum, Catheryn M. Yashar, Kristin Bradley, Susana M. Campos, Junzo Chino, Hye Sook Chon, Christina Chu, David Cohn, Marta Ann Crispens, Shari Damast, Elisabeth Diver, Christine M. Fisher, Peter Frederick, David K. Gaffney, Suzanne George, Robert Giuntoli, Ernest Han, Brooke Howitt, Warner K. Huh, Jayanthi Lea, Andrea Mariani, David Mutch, Larissa Nekhlyudov, Mirna Podoll, Steven W. Remmenga, R. Kevin Reynolds, Ritu Salani, Rachel Sisodia, Pamela Soliman, Edward Tanner, Stefanie Ueda, Renata Urban, Stephanie L. Wethington, Emily Wyse, Kristine Zanotti, Nicole R. McMillian, Angela D. Motter
Journal: Journal of the National Comprehensive Cancer Network (2021)

The NCCN Guidelines for Uterine Neoplasms provide recommendations for diagnostic workup, clinical staging, and treatment options for patients with endometrial cancer or uterine sarcoma. These NCCN Guidelines Insights focus on the recent addition of molecular profiling information to aid in accurate diagnosis, classification, and treatment of uterine sarcomas.
Determinants for hospitalisations, intensive care unit admission and death among 20,293 reported COVID-19 cases in Portugal, March to April 2020
Authors: Vasco Ricoca Peixoto, André Vieira, Pedro Aguiar, Paulo Sousa, Carlos Carvalho, Daniel Thomas, Alexandre Abrantes, Carla Nunes
Journal: Eurosurveillance (2021)

BackgroundDeterminants of hospitalisation, intensive care unit (ICU) admission and death are still unclear for COVID-19. Few studies have adjusted for confounding for different clinical outcomes including all reported cases within a country.AimWe used routine surveillance data from Portugal to identify risk factors for severe COVID-19 outcomes, and to support risk stratification, public health interventions, and planning of healthcare resources.MethodsWe conducted a retrospective cohort study including 20,293 laboratory-confirmed cases of COVID-19 reported between 1 March and 28 April 2020 through the national epidemiological surveillance system. We calculated absolute risk, relative risk (RR) and adjusted relative risk (aRR) to identify demographic and clinical factors associated with hospitalisation, ICU admission and death using Poisson regressions.ResultsIncreasing age (≥ 60 years) was the major determinant for all outcomes. Age ≥ 90 years was the strongest determinant of hospital admission (aRR: 6.1), and 70-79 years for ICU (aRR: 10.4). Comorbidities of cardiovascular, immunodeficiency, kidney and lung disease (aRR: 4.3, 2.8, 2.4, 2.0, respectively) had stronger associations with ICU admission, while for death they were kidney, cardiovascular and chronic neurological disease (aRR: 2.9, 2.6, 2.0).ConclusionsOlder age was the strongest risk factor for all severe outcomes. These findings from the early stages of the COVID-19 pandemic support risk-stratified public health measures that should prioritise protecting older people. Epidemiological scenarios and clinical guidelines should consider this, even though under-ascertainment should also be considered.
Addressing Transplant Candidacy When Evaluating Safety of Direct Oral Anticoagulant Agents in Patients on Hemodialysis
Authors: Eliot Heher, Nahel Elias
Journal: Journal of the American Society of Nephrology (2021)

In their analysis of the subgroup of patients on hemodialysis in the Valkyrie study,[1][1] De Vriese et al. do not directly address the risks and benefits of rivaroxaban in patients on dialysis who are candidates for kidney transplantation. Direct oral anticoagulant agents (DOACs) may affect
Cerebral venous thrombosis and myeloproliferative neoplasms: A three‐center study of 74 consecutive cases
Authors: Naseema Gangat, Paola Guglielmelli, Silvia Betti, Faiqa Farrukh, Alessandra Carobbio, Tiziano Barbui, Alessandro M. Vannucchi, Valerio De Stefano, Ayalew Tefferi
Journal: American Journal of Hematology (2021)

The recent association of cerebral venous thrombosis (CVT) with COVID-19 vaccinations prompted the current retrospective review of 74 cases of CVT (median age = 44 years, range 15-85; 61% females) associated with myeloproliferative neoplasms (MPNs), seen at the Mayo Clinic, Catholic University of Rome, and University of Florence, between 1991 and 2021. Disease-specific frequencies were 1.3% (39/2893), 1.2% (21/1811) and 0.2% (3/1888) for essential thrombocythemia, polycythemia vera and primary myelofibrosis, respectively. Cerebral venous thrombosis occurred either prior to (n = 20, 27%), at (n = 32, 44%) or after (n = 22) MPN diagnosis. A total of 72% of patients presented with headaches. Transverse (51%), sagittal (43%) and sigmoid sinuses (35%) were involved with central nervous system hemorrhage noted in 10 (14%) patients. In all, 91% of tested patients harbored JAK2V617F. An underlying thrombophilic condition was identified in 19 (31%) cases and history of thrombosis in 10 (14%). Treatment for CVT included systemic anticoagulation alone (n = 27) or in conjunction with aspirin (n = 24), cytoreductive therapy (n = 14), or both (n = 9). At a median follow-up of 5.1 years (range 0.1-28.6), recurrent CVT was documented in three (4%) patients while recurrent arterial and venous thromboses and major hemorrhage were recorded in 11%, 9% and 14%, respectively. Follow-up neurological assessment revealed headaches (n = 9), vision loss (n = 1) and cognitive impairment (n = 1). The current study lends clarity to MPN-associated CVT and highlights its close association with JAK2V617F, younger age and female gender. Clinical features that distinguish COVID vaccine-related CVT from MPN-associated CVT include, in the latter, lower likelihood of concurrent venous thromboses and intracerebral hemorrhage; as a result, MPN-associated CVT was not fatal.
Abstract PS12-11: Phase 1b clinical trial of HX008, a novel anti-PD-1 monoclonal antibody, Combined with gemcitabine and cisplatin in the first-line treatment of metastatic triple-negative breast cancer
Authors: Xichun Hu, Jun Cao, Biyun Wang, Jian Zhang, Leiping Wang, Zhonghua Tao, Ting Li
Journal: Cancer Research (2021)

Abstract Background HX008 is a humanized IgG4S228P anti-PD-1 monoclonal antibody with an engineered Fc domain. Gemcitabine plus cisplatin (GP) has shown satisfying antitumor activity as first-line therapy for metastatic triple-negative breast cancer (mTNBC) in CBCSG 006 trial (ClinicalTrials.gov, NCT01287624). The phase 1b study was conducted to assess the safety and preliminary antitumor activity of HX008, combined with GP in patients with mTNBC in first-line setting. Methods Eligible patients are mTNBC with ≥6 months DFI who never receive antitumor therapy for metastatic disease. Participants received HX008 at 3mg/kg (d1, q3w) plus gemcitabine at 1250mg/m2 (d1, 8, q3w) and cisplatin 75mg/m2 (d1, q3w). At most 6 cycles of GP chemotherapy were given, while HX 008 could be maintained until disease progression or unacceptable toxicity occurred. Results Between July 2019 and March 2020, a total of 31 patients were enrolled in this study. Median (range) age was 50 (29-69) years. Among 31 patients who were evaluated, 25 (80.6%) experienced objective response and the other 6 (19.4%) experienced stable disease (SD). The median progression free survival (PFS) was 9.07 months (95%CI,7.29m-13.01m). The PFS data was not yet mature, for nearly half of the intent-to-treat population has not progressed by October 9, 2020. The most common treatment-related adverse events of grade 3 or 4 included neutropenia (71.0%), anemia (55.5%), thrombocytopenia (32.3%), hypocalcemia (9.68%), hypokalemia (6.45%), and Alanine aminotransferase increased (6.45%). There were no treatment-related deaths. Conclusion HX008 plus GP demonstrated promising activity and manageable safety in patients with mTNBC in first-line setting. Clinical trial information: CHINADRUGTRIALS.ORG, CTR 20191353. Citation Format: Xichun Hu, Jun Cao, Biyun Wang, Jian Zhang, Leiping Wang, Zhonghua Tao, Ting Li. Phase 1b clinical trial of HX008, a novel anti-PD-1 monoclonal antibody, Combined with gemcitabine and cisplatin in the first-line treatment of metastatic triple-negative breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS12-11.
28563 Risankizumab as an efficient therapy for psoriatic patients in long term: Analysis of 3 cases with a maintenance dose every 16 weeks.
Authors: Antonio Martorell, Maria Solera, Virginia Sanz-Motilva, Maria Luisa Garcia-Melgares, Luis Hueso, Jose Luis Rueda, Gema Ochando, Cristina Pelufo, Marta Borras, Alberto Alfaro
Journal: Journal of the American Academy of Dermatology (2021)
Cell-matrix reciprocity in 3D culture models with nonlinear elasticity
Authors: Kaizheng Liu, Maury Wiendels, Hongbo Yuan, Changshun Ruan, Paul H.J. Kouwer
Journal: Bioactive Materials (2021)

Three-dimensional (3D) matrix models using hydrogels are powerful tools to understand and predict cell behavior. The interactions between the cell and its matrix, however is highly complex: the matrix has a profound effect on basic cell functions but simultaneously, cells are able to actively manipulate the matrix properties. This (mechano)reciprocity between cells and the extracellular matrix (ECM) is central in regulating tissue functions and it is fundamentally important to broadly consider the biomechanical properties of the in vivo ECM when designing in vitro matrix models. This manuscript discusses two commonly used biopolymer networks, i.e. collagen and fibrin gels, and one synthetic polymer network, polyisocyanide gel (PIC), which all possess the characteristic nonlinear mechanics in the biological stress regime. We start from the structure of the materials, then address the uses, advantages, and limitations of each material, to provide a guideline for tissue engineers and biophysicists in utilizing current materials and also designing new materials for 3D cell culture purposes.
Case 26-2021: A 49-Year-Old Man with Relapsed Acute Myeloid Leukemia
Authors: Andrew M. Brunner, Richard A. Newcomb, Yi-Bin Chen, Andrew M. Crabbe
Journal: New England Journal of Medicine (2021)

A 49-year-old man was evaluated because of relapsed acute myeloid leukemia that occurred 14 months after the initial diagnosis and treatment. Molecular genetic profiling at the time of relapse identified a new internal tandem duplication mutation in FLT3 (FLT3-ITD). A bone marrow biopsy was performed, and management decisions were made.
Cystic Fibrosis and the Cells of the Airway Epithelium: What Are Ionocytes and What Do They Do?
Authors: Viral S. Shah, Raghu R. Chivukula, Brian Lin, Avinash Waghray, Jayaraj Rajagopal
Journal: Annual Review of Pathology Mechanisms of Disease (2021)

Cystic fibrosis (CF) is caused by defects in an anion channel, the cystic fibrosis transmembrane conductance regulator (CFTR). Recently, a new airway epithelial cell type has been discovered and dubbed the pulmonary ionocyte. Unexpectedly, these ionocytes express higher levels of CFTR than any other airway epithelial cell type. However, ionocytes are not the sole CFTR-expressing airway epithelial cells, and CF-associated disease genes are in fact expressed in multiple airway epithelial cell types. The experimental depletion of ionocytes perturbs epithelial physiology in the mouse trachea, but the role of these rare cells in the pathogenesis of human CF remains mysterious. Ionocytes have been described in diverse tissues(kidney and inner ear) and species (frog and fish). We draw on these prior studies to suggest potential roles of airway ionocytes in health and disease. A complete understanding of ionocytes in the mammalian airway will ultimately depend on cell type–specific genetic manipulation
Selenium–GPX4 axis protects follicular helper T cells from ferroptosis
Authors: Yin Yao, Zhian Chen, Hao Zhang, Cailing Chen, Ming Zeng, Joseph Yunis, Yunbo Wei, Yanmin Wan, Naiqi Wang, Mingzhe Zhou, Chao Qiu, Qunxiong Zeng, Hong Sheng Ong, Hao Wang, Fadzai Victor Makota, Yang Yang, Zhaohui Yang, Nan Wang, Jun Deng, Chao Shen, Yan Xia, Lin Yuan, Zhaoqin Lian, Yike Deng, Cuilian Guo, Ao Huang, Pengcheng Zhou, Haibo Shi, Weitian Zhang, Hongliang Yi, Dongmei Li, Ming Xia, Jing Fu, Ning Wu, Judy B. de Haan, Nan Shen, Wenhong Zhang, Zheng Liu, Di Yu
Journal: Nature Immunology (2021)
Valuation of Cavities in the Lungs Among HIV/TB Patients
Authors: I. Yu. Masterova, S. Yu. Degtyareva, A. N. Narkevich, L. A. Shlykova, E. V. Zaitseva, P. V. Gavrilov
Journal: Radiology - Practice (2021)

Early diagnosis of respiratory tuberculosis among HIV-infected patients improves the prognosis of recovery and reduces mortality. The emergence of cavities is one of the patterns of the progression of pulmonary tuberculosis. The article analyzes the results of examination of HIV-infected tuberculosis patients with cavities. We estimate the data of anamnesis, the disease clinic and immune status. The retrospective study included patients of the Leningrad region with HIV/TB with early respiratory tuberculosis from 2014 to 2016 (n = 852). We identified a clear relationship between chemoprophylaxis and antiretroviral therapy on developing tuberculosis non-cavity, but no direct relationship was found with widespread or disseminated TB. We also obtained a significantly relationship between the bacterial excretion and the detection of destruction in the lung tissue on the background a pronounced decrease in the immune status (CD4 100 cells/μl or less). There are statistically significant decreases in the frequency of cavities of respiratory tuberculosis and the proportion of etiologically verified cases is in case in the suppression of immunity (CD4 100 cells/μl or less). However, the relationship between early mortality from tuberculosis (during the first year) and pulmonary tuberculosis with cavities was not obtained.
27050 Efficacy of baricitinib 2-mg stratified by baseline body surface area in adults with moderate-to-severe atopic dermatitis
Authors: Jonathan I. Silverberg, Mark Boguniewicz, Jill Waibel, Jamie Weisman, Lindsey Strowd, Luna Sun, Yuxin Ding, Orin Goldblum, Fabio P. Nunes, Eric L. Simpson
Journal: Journal of the American Academy of Dermatology (2021)
New USPSTF Recommendations for Screening for Prediabetes and Type 2 Diabetes
Authors: Edward W. Gregg, Tannaz Moin
Journal: JAMA (2021)

Li Wang, PhD; Xiaoguang Li, PhD; Zhaoxin Wang, PhD; Michael P. Bancks, PhD; Mercedes R. Carnethon, PhD; Philip Greenland, MD; Ying-Qing Feng, MD; Hui Wang, MD, PhD; Victor W. Zhong, PhD
Human reference gut microbiome catalog including newly assembled genomes from under-represented Asian metagenomes
Authors: Chan Yeong Kim, Muyoung Lee, Sunmo Yang, Kyungnam Kim, Dongeun Yong, Hye Ryun Kim, Insuk Lee
Journal: Genome Medicine (2021)

Abstract Background Metagenome sampling bias for geographical location and lifestyle is partially responsible for the incomplete catalog of reference genomes of gut microbial species. Thus, genome assembly from currently under-represented populations may effectively expand the reference gut microbiome and improve taxonomic and functional profiling. Methods We assembled genomes using public whole-metagenomic shotgun sequencing (WMS) data for 110 and 645 fecal samples from India and Japan, respectively. In addition, we assembled genomes from newly generated WMS data for 90 fecal samples collected from Korea. Expecting genome assembly for low-abundance species may require a much deeper sequencing than that usually employed, so we performed ultra-deep WMS (&gt; 30 Gbp or &gt; 100 million read pairs) for the fecal samples from Korea. We consequently assembled 29,082 prokaryotic genomes from 845 fecal metagenomes for the three under-represented Asian countries and combined them with the Unified Human Gastrointestinal Genome (UHGG) to generate an expanded catalog, the Human Reference Gut Microbiome (HRGM). Results HRGM contains 232,098 non-redundant genomes for 5414 representative prokaryotic species including 780 that are novel, &gt; 103 million unique proteins, and &gt; 274 million single-nucleotide variants. This is an over 10% increase from the UHGG. The new 780 species were enriched for the Bacteroidaceae family, including species associated with high-fiber and seaweed-rich diets. Single-nucleotide variant density was positively associated with the speciation rate of gut commensals. We found that ultra-deep sequencing facilitated the assembly of genomes for low-abundance taxa, and deep sequencing (e.g., &gt; 20 million read pairs) may be needed for the profiling of low-abundance taxa. Importantly, the HRGM significantly improved the taxonomic and functional classification of sequencing reads from fecal samples. Finally, analysis of human self-antigen homologs on the HRGM species genomes suggested that bacterial taxa with high cross-reactivity potential may contribute more to the pathogenesis of gut microbiome-associated diseases than those with low cross-reactivity potential by promoting inflammatory condition. Conclusions By including gut metagenomes from previously under-represented Asian countries, Korea, India, and Japan, we developed a substantially expanded microbiome catalog, HRGM. Information of the microbial genomes and coding genes is publicly available ( www.mbiomenet.org/HRGM/ ). HRGM will facilitate the identification and functional analysis of disease-associated gut microbiota.
27995 Evaluation of the modified immune prognostic index to prognosticate outcomes in metastatic uveal melanoma patients treated with immune checkpoint inhibitors
Authors: Michael Sander, Igor Stukalin, Isabelle A. Vallerand, Siddhartha Goutam, Benjamin W. Ewanchuk, Daniel E. Meyers, Aliyah Pabani, Don Morris, Daniel Y.C. Heng, Tina Cheng
Journal: Journal of the American Academy of Dermatology (2021)
Restoring mammary gland structures and functions with autogenous cell therapy
Authors: Dandan Zhang, Guodong Wang, Liangshan Qin, Quanhui Liu, Shaoqian Zhu, Sheng Ye, Xiaobo Li, Yulian Wu, Yanan Hu, Shulin Liu, Yafei Jiao, Longfei Sun, Danwei Lv, Jiawen Ma, Man Luo, Mengcheng Yao, Mengmei Li, Lei Zhou, Surui Pei, Lanyu Li, Deshun Shi, Ben Huang
Journal: Biomaterials (2021)
Preventing a Pandemic's Toll—We've Been Here Before
Authors: Abigail Zuger
Journal: JAMA (2021)

Preventing a Pandemic's Toll-We've Been Here Before No 2 epidemics are alike; those who practiced medicine in the early days of HIV/AIDS can attest to that.AIDS back then was an ultramarathon; COVID is more a series of exhausting sprints.Even so, history is repeating itself in an uncanny fashion as clinicians struggle once again to convince patients to save their own lives.Widespread rejection of COVID vaccination has been ascribed to specific contemporary problems: the fraught political climate, an established "anti-vaxx" movement, these vaccines' novel mechanisms, and their unusually rapid path to market.In the late '90s, though, the first effective HIV treatments sometimes were met with a very similar reception.No older HIV doctor will ever forget the watershed year of 1996, when the lifesaving power of specific antiretroviral combinations became clear.With those daily handfuls of capsules and pills, emaciated patients began to thrive, all the implicit promises of modern medicine suddenly visible in their solid flesh and blood.Many HIV-infected people clamored for these medications.They saw friends and relatives transformed, or they just trusted our promises.Others, however, could not be convinced to go near them.The AIDS drugs were poisons, unnatural, and toxic, they said.The drugs were still experimental-so thanks, but no thanks!The drugs were for sick, dying people, not vigorous people like them.(They were going to
Predictors of Rheumatic <scp>Immune‐Related</scp> Adverse Events and De Novo Inflammatory Arthritis After Immune Checkpoint Inhibitor Treatment for Cancer
Authors: Amy Cunningham‐Bussel, Jiaqi Wang, Lauren C. Prisco, Lily W. Martin, Kathleen M. M. Vanni, Alessandra Zaccardelli, Mazen Nasrallah, Lydia Gedmintas, Lindsey A. MacFarlane, Nancy A. Shadick, Mark M. Awad, Osama Rahma, Nicole R. LeBoeuf, Ellen M. Gravallese, Jeffrey A. Sparks
Journal: Arthritis & Rheumatology (2021)

To identify predictors of rheumatic immune-related adverse events (irAEs) following immune checkpoint inhibitor (ICI) treatment for cancer.
Immunochemotherapy as First-line Treatment for Locally Advanced or Metastatic Squamous Non–Small Cell Lung Cancers—Reply
Authors: Jie Wang, Shiang Jiin Leaw, Shun Lu
Journal: JAMA Oncology (2021)

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