tbuckley/cabot-search huggingface dataset:
Why is India having a covid-19 surge?
Authors: Kamala Thiagarajan
Journal: BMJ (2021)

Why is India having a covid-19 surge?India's infections set new pandemic records in April, with more than 300 000 positive tests each day for a week.Kamala Thiagarajan looks at the many unanswered questions Kamala ThiagarajanOn 26 April India saw the highest daily tally of new SARS-CoV-2 infections ever recorded in the world, 360 960, taking its pandemic total to 16 million cases, second only to the US, and more than 200 000 deaths.The devastating second wave comes a year after the country imposed one of the most rigid lockdown restrictions in the world-and just three months since its health ministry declared that infections and mortality were at an all time low.
Efficacy and safety of voclosporin versus placebo for lupus nephritis (AURORA 1): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial
Authors: Brad H Rovin, Y K Onno Teng, Ellen M Ginzler, Cristina Arriens, Dawn J Caster, Juanita Romero-Diaz, Keisha Gibson, Joshua Kaplan, Laura Lisk, Sandra Navarra, Samir V Parikh, Simrat Randhawa, Neil Solomons, Robert B Huizinga
Journal: The Lancet (2021)
A synthetically lethal nanomedicine delivering novel inhibitors of polynucleotide kinase 3′-phosphatase (PNKP) for targeted therapy of PTEN-deficient colorectal cancer
Authors: Sams M.A. Sadat, Igor M. Paiva, Zahra Shire, Forughalsadat Sanaee, Timothy D.R. Morgan, Marco Paladino, Feridoun Karimi-Busheri, Rajam S. Mani, Gary R. Martin, Frank R. Jirik, Dennis G. Hall, Michael Weinfeld, Afsaneh Lavasanifar
Journal: Journal of Controlled Release (2021)

Phosphatase and TENsin homolog deleted on chromosome 10 (PTEN) is a major tumor-suppressor protein that is lost in up to 75% of aggressive colorectal cancers (CRC). The co-depletion of PTEN and a DNA repair protein, polynucleotide kinase 3′-phosphatase (PNKP), has been shown to lead to synthetic lethality in several cancer types including CRC. This finding inspired the development of novel PNKP inhibitors as potential new drugs against PTEN-deficient CRC. Here, we report on the in vitro and in vivo evaluation of a nano-encapsulated potent, but poorly water-soluble lead PNKP inhibitor, A83B4C63, as a new targeted therapeutic for PTEN-deficient CRC. Our data confirmed the binding of A83B4C63, as free or nanoparticle (NP) formulation, to intracellular PNKP using the cellular thermal shift assay (CETSA), in vitro and in vivo. Dose escalating toxicity studies in healthy CD-1 mice, based on measurement of animal weight changes and biochemical blood analysis, revealed the safety of both free and nano-encapsulated A83B4C63, at assessed doses of ≤50 mg/kg. Nano-carriers of A83B4C63 effectively inhibited the growth of HCT116/PTEN−/− xenografts in NIH-III nude mice following intravenous (IV) administration, but not that of wild-type HCT116/PTEN+/+ xenografts. This was in contrast to IV administration of A83B4C63 solubilized with the aid of Cremophor EL: Ethanol (CE), which led to similar tumor growth to that of formulation excipients (NP or CE without drug) or 5% dextrose. This observation was attributed to the higher levels of A83B4C63 delivered to tumor tissue by its NP formulation. Our data provide evidence for the success of NPs of A83B4C63, as novel synthetically lethal nano-therapeutics in the treatment of PTEN-deficient CRC. This research also highlights the potential of successful application of nanomedicine in the drug development process.
Abstract 16146: Trends in Heart Disease Mortality by Subtype in Black and White Men and Women in The United States, 1999-2017
Authors: Nilay S Shah, Rebecca Molsberry, Donald M Lloyd-Jones, Mercedes R Carnethon, Sadiya S Khan
Journal: Circulation (2019)

Introduction: Declines in heart disease mortality rates have slowed in the U.S. However, deaths due to HD are heterogeneous and trends may not be consistent across HD subtypes or by race and sex. W...
EXOSOMAL MICRORNAS DISTINGUISH PATIENTS WITH HEART FAILURE WITH PRESERVED EJECTION FRACTION IDENTIFIED BY EXERCISE RIGHT HEART CATHETERIZATION
Authors: Dhivya Vadhana Meenakshi Siddharthan, Skylar A Rizzo, D. Kent Arrell, Timothy E Peterson, Paul G Stalboerger, Andre Terzic, Barry Borlaug, Atta Behfar
Journal: Journal of the American College of Cardiology (2021)
CO-EXISTING PROTEIN ENERGY MALNUTRITION IS ASSOCIATED WITH INCREASED MORTALITY IN PATIENTS ADMITTED FOR SURGICAL AORTIC VALVE REPLACEMENT ANALYSIS OF THE NATIONAL INPATIENT SAMPLE
Authors: Emmanuel Akuna, Iriagbonse Asemota, Smriti Khanal, Raquel Soon-Shion, Muhammad Usman Almani, Dimeji Williams, Elbermawy Mahmoud, Muhammad Usman, Sharma Bharosa, Cyra Kang, Maghari Ibrahim
Journal: Journal of the American College of Cardiology (2021)
A DISSECTING INTRAMURAL LEFT VENTRICULAR HEMATOMA, CASE REPORT
Authors: Ahmed Shahin, Amr El Sheikh, Mohamed Abdelrazek, Mahmoud Khalil, Ahmed Gouda, Sara El Sharkawy, Asmaa Ramadan, Mohamed Hegab, Hesham ElZomor, Osama Shoeib
Journal: Journal of the American College of Cardiology (2021)
PULMONARY ARTERY TO AORTA DIAMETER RATIO DERIVED FROM LUNG CANCER SCREENING CT IS ASSOCIATED WITH ALL-CAUSE MORTALITY
Authors: Hojune Chung, Malika Ramani, Dhairyasheel Ghosalkar, Alice Chu, Wen-Chih Wu, Gaurav Choudhary, Alan Morrison
Journal: Journal of the American College of Cardiology (2021)
IMPROVING TRANSCATHETER AORTIC VALVE REPLACEMENT OUTCOMES IN BICUSPID AORTIC VALVES THROUGH A PREOPERATIVE COMPUTATIONAL APPROACH
Authors: Breandan Yeats, Sri Krishna Sivakumar, Venkateshwar Polsani, Pradeep Yadav, Vinod Thourani, Lakshmi Dasi
Journal: Journal of the American College of Cardiology (2021)
INSULIN RESISTANCE INDEPENDENTLY PREDICTS HYPERTENSION IN INDIVIDUALS WITH LOWER EDUCATION STATUS - FROM THE ELSA-BRASIL COHORT STUDY
Authors: Luisa Lima Castro Schutze, Luisa Brant, Maria de Fátima Haueisen Sander Diniz, Paulo Lotufo, Isabela Bensenor, Rosane Harter Griep, Sandhi Barreto, Antonio Ribeiro
Journal: Journal of the American College of Cardiology (2021)
Change in Myocardial Contractility in Response to Treatment with Norepinephrine in Septic Shock
Authors: Francesca Innocenti, Vittorio Palmieri, Irene Tassinari, Elisa Capretti, Anna De Paris, Adriana Gianno, Anna Marchesini, Michele Montuori, Riccardo Pini
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

"Change in Myocardial Contractility in Response to Treatment with Norepinephrine in Septic Shock." American Journal of Respiratory and Critical Care Medicine, 204(3), pp. 365–368
ASSOCIATION OF VENTRICULAR ARRHYTHMIA WITH OUTCOMES IN FEMALES WITH PERIPARTUM CARDIOMYOPATHY. A STUDY FROM NATIONAL INPATIENT SAMPLE 2016
Authors: Kashyap Shah, Harshith Thyagaturu, Vivek Modi, Haresh Gandhi, Mohsin Mughal, Marc Kervin Antoine, Marc Katz, Chris Cutitta
Journal: Journal of the American College of Cardiology (2021)
CLINICAL PHENOTYPE OF PATIENTS WITH HEART FAILURE WITH STABLE MID-RANGE EJECTION FRACTION IN COMPARISON TO PATIENTS WITH HEART FAILURE WITH STABLE REDUCED EJECTION FRACTION AND HEART FAILURE WITH STABLE PRESERVED EJECTION FRACTION
Authors: Mohamad Khaled Soufi, Rishabh R. Jain, Joseph R. McFarland, Simon Pinsky, Milin N. Rana, Alexander Dang, Wissam Khalife
Journal: Journal of the American College of Cardiology (2021)
Crosstalk between microRNA expression and DNA methylation drives the hormone-dependent phenotype of breast cancer
Authors: Miriam Ragle Aure, Thomas Fleischer, Sunniva Bjørklund, Jørgen Ankill, Jaime A. Castro-Mondragon, Anne-Lise Børresen-Dale, Jörg Tost, Kristine K. Sahlberg, Anthony Mathelier, Xavier Tekpli, Vessela N. Kristensen
Journal: Genome Medicine (2021)

Abnormal DNA methylation is observed as an early event in breast carcinogenesis. However, how such alterations arise is still poorly understood. microRNAs (miRNAs) regulate gene expression at the post-transcriptional level and play key roles in various biological processes. Here, we integrate miRNA expression and DNA methylation at CpGs to study how miRNAs may affect the breast cancer methylome and how DNA methylation may regulate miRNA expression.
We need clinical guidelines fit for a pandemic
Authors: Dipender Gill, Emma H Baker, Andrew W Hitchings
Journal: BMJ (2021)

The covid-19 pandemic unleashed itself onto healthcare services at pace.Evidence evolved, 1 2 opinions conflicted, 3 and both real and perceived resource constraints were confronted. 4Against this backdrop, clinicians had to make time-critical decisions about what treatments to offer, or not, to their patients.Working groups were hastily convened, but much of the decision making happened at the bedside.Undoubtedly, many tackled the same questions simultaneously but reached different answers.Centrally produced guidance was conspicuously slow to emerge.For example, by the time the National Institute for Health and Care Excellence (NICE) published a guideline on the management of covid-19 on 23 March 2021, 5 UK clinicians had managed more than 450 000 hospital admissions related to the disease.
Molecular genetic tests in surgical management of familial adenomatous polyposis (multiple letters) [3]
Authors: H. F.A. Vasen, R. B. Van der Luijt, C. Tops, J. F.M. Slors, D. G.R. Evans, J. Hill, T. Dudding, J. Burn, E. R. Maher
Journal: The Lancet (1998)
PULMONARY EMBOLIC PROTECTION USING A VENOUS ENDOPROSTHESIS WALLSTENT™ IN MECHANICAL THROMBECTOMY FOR ACUTE DEEP VENOUS THROMBOSIS
Authors: Christopher Mahida, Obadah Aqtash, Khalil Anouti, Amer Sayed, Fahad Waqar
Journal: Journal of the American College of Cardiology (2021)
THE IMPACT OF SIROLIMUS AS A PRIMARY IMMUNOSUPPRESSANT ON MYOCARDIAL FIBROSIS AND DIASTOLIC FUNCTION FOLLOWING HEART TRANSPLANTATION
Authors: Hilmi Alnsasra, Rabea Asleh, Jae Oh, Joseph Maleszewski, Amir Lerman, Takumi Toya, Krishnaswamy Chandrasekaran, Melanie Bois, Sudhir Kushwaha
Journal: Journal of the American College of Cardiology (2021)
Partha Kar: “Phir Bhi Dil Hai Hindustani”—the anguish of the Indian diaspora
Authors: Partha Kar
Journal: BMJ (2021)

I have a strong sense of deja vu, witnessing the scenes of carnage in India as covid rips through the country. Perhaps I’m feeling the pain more intensely because, having seen the impact that covid had in January in the country where I live, I’m now seeing it replicated in the country where my heart lies.

Thousands in the Indian diaspora—especially those working in the NHS—are watching with similar, heart wrenching anguish and worry about families and friends. It’s frustrating, as somehow India seemed to have dodged the bullet the first time around. Yet a toxic mixture of political myopia, religious sentiments, and perhaps a degree of overconfidence has culminated in a mostly self-inflicted rise of covid-19 and …
I Am Concerned About Osteoporosis: What Do I Need to Know?
Authors: Katie L. Kaput, Vishnu Sundaresh
Journal: JAMA Internal Medicine (2021)

What Is Osteoporosis?Osteoporosis is a medical condition that causes bones to become weak and thin, making them more likely to fracture.Risk for fractures is increased in many bones, particularly those of the hip and spine.Fractures can lead to pain, disability, loss of independence, and even death.Osteoporosis does not cause symptoms, and many people with osteoporosis may not be aware that they have it.It is common, affecting more than 10 million Americans.
A REAL-WORLD ASSESSMENT OF PATIENT CHARACTERISTICS AND TREATMENT PATTERNS AMONG PATIENTS WITH LIPOPROTEIN(A) MEASUREMENT AND RECEIVING PRIMARY AND SECONDARY PREVENTION FOR CARDIOVASCULAR DISEASE IN THE US
Authors: Raju Gautam, Rina Mehta, Diana Amari, Jihaeng Heo, Siwei Wang, Jennifer C. Sung, Joaquim Cristino, Nathan Wong
Journal: Journal of the American College of Cardiology (2021)
JOINT PAINS AND A RACING HEART- VENTRICULAR TACHYCARDIA AS AN INITIAL PRESENTATION OF UNDERLYING SCLERODERMA RELATED AUTOIMMUNE MYOCARDITIS
Authors: Ro-Kaye Simmonds, Munder Abuaisha, Ross Lavine, Zachary Banbury, Michael Basir, Anna-Belle Robertson, Aalap Chokshi
Journal: Journal of the American College of Cardiology (2021)
Simultaneous improvement to solubility and bioavailability of active natural compound isosteviol using cyclodextrin metal-organic frameworks
Authors: Xiaojin Chen, Tao Guo, Kaikai Zhang, Jiacai Chen, Caifen Wang, Xiaohong Ren, Qin Wang, Yingchao Yang, Chongjing Liu, Wen Tan, Shuangying Gui, Li Wu, Jiwen Zhang
Journal: Acta Pharmaceutica Sinica B (2021)

Cyclodextrin metal-organic framework (CD-MOF) as a highly porous supramolecular carrier could be one of the solutions to the insolubility of isosteviol (STV). The solubility of STV was lower than 20.00 ng/mL at pH 1.0 and pH 4.5, whilst its solubility increased to 20,074.30 ng/mL at pH 6.8 and 129.58 ng/mL in water with a significant pH-dependence. The in vitro release profiles of STV from [email protected] (0.5:1) were pH-independent in distinct pH media and closed to be thoroughly released but no such release profiles were observed for [email protected] (1:1) owing to nanoclusters formation. The bioavailability of [email protected] (1:1) in rats was 8.67-fold higher than that of STV, and was 1.32- and 1.27-fold higher than that of [email protected] and [email protected] (0.5:1). Our results indicated that the inclusion mechanism played a primary role when STV in CD-MOF was at a low loading ratio, while the increasement in bioavailability at a high loading ratio, which was attributed to the nanocluster mechanism. This was confirmed by molecular simulation. In conclusion, CD-MOF is a promising system for STV loading, overcoming the insolubility and to improve the bioavailability of this natural compound.
Contributions of immigrants to biomedical research in the US: a personal reflection
Authors: Sophie Paczesny
Journal: Journal of Clinical Investigation (2021)

Innovative progress depends on the degree of our collective differences. Immigrants bring unique experiences and perspectives that can diversify how we as a community approach problems. There are many successful immigrants in the biomedical research field. The percentage of naturalized citizens in the biomedical workforce has grown from 8% to 18% in just the last decade. Of the Americans who have won Nobel Prizes in Chemistry, Medicine, and Physics, 35% were immigrants. This number may be an underestimate, as it does not include winners who immigrated to America after receiving their prizes, such as Albert Einstein. This trend has accelerated over the years;from 1901 to 1959, nine immigrants to the US won Nobel Prizes in Medicine compared with 29 immigrants from 1960 to 2019. Here, Paczesny discusses the immigrants contributions to biomedical research in all Western countries.
MEDICAL STUDENT LEADERSHIP GROUP CONVENED BY THE AMERICAN COLLEGE OF CARDIOLOGY
Authors: Samip Sheth, Adriana Mares, Gurleen Kaur, Sagarika Arogyaswamy, Emily Gates, Anthony Maltagliati, Kevin Paternostro, Selen Uman, Melissa Walsh, Erin Falk, Zachary Manna
Journal: Journal of the American College of Cardiology (2021)
OXIDIZED LOW-DENSITY LIPOPROTEIN EXACERBATES NIVOLUMAB-INDUCED CARDIOTOXICITY BY MODULATING TLR4/NF-KB AND NLRP3 PATHWAYS
Authors: Nicola Maurea, Andrea Paccone, Martina Iovine, Fabrizio Maurea, Gerardo Botti, Vincenzo Quagliariello
Journal: Journal of the American College of Cardiology (2021)
Expression of enhancer of zeste homolog 2 in renal cell carcinoma and relationship to downregulation of micro RNA-101.
Authors: T. Sakurai, V. Bilim, K. Yuuki, M. Tsukigi, A. V. Ougolkov, Y. Tomita
Journal: Journal of Clinical Oncology (2010)

4622 Background: Enhancer of zeste homolog 2 (EZH2), a subunit of polycomb repressive complex 2(PRC2), is commonly associated with gene silencing. It has already been reported that EZH2 is overexpressed in various cancer, including prostate, breast and pancreatic. It was also reported that EZH2 transcripts levels were higher in renal cell carcinoma (RCC) than in normal kidney. Database search returned EZH2 as a highly conserved target of micro RNA miR-101. Our objectives were to determine the expression pattern of EZH2 in RCC and to search for possible mechanism of its dysregulation. Furthermore, we tried to search genes which are donwregulated by EZH2 in RCC resulting in higher malignant character of the tumors. Methods: Immunohistochemistry and cytosolic/nuclear fractionation were performed to determine the expression pattern of EZH2. We used quantitative RT-PCR to examine the expression levels of miR-101 in RCC cell lines, and RCC tissues. RNA interference, Western blotting, were applied to study the effect of EZH2 genetic depletion on downstream genes products and renal cancer cell proliferation. Results: We detected nuclear overexpression of EZH2 in all 8 RCC cell lines and in 53 of 58 (91%) cases of human RCC whereas no nuclear accumulation was detected in normal kidney. MiR-101 expression was drastically decreased in all cell lines and tumor tissues compared with normal kidney. When we transfected cell lines with siRNA targeting EZH2 or miR-101 precursor, we observed EZH2 downregulation, decreased H3 methylation and upregulation of p27kip1. This was accompanied with diminished cellular viability. Conclusions: Our results demonstrate nuclear accumulation of EZH2 as a marker of human RCC, identify that EZH2 positively regulates RCC cell survival and proliferation via inhibition of at least p27kip1 tumor suppressing gene and suggest EZH2 as a potential therapeutic target in the treatment of human renal cancer. No significant financial relationships to disclose.
NON-INVASIVE EVALUATION OF AORTIC PRESSURE, FLOW AND VALVULO-ARTERIAL LOAD IN PATIENTS WITH AORTIC STENOSIS BEFORE AND AFTER TRANSCATHETER AORTIC VALVE REPLACEMENT
Authors: Ning Song, Audrey Adji, Sara Hungerford, Mayooran Namasivayam, Christopher Hayward, Andrew Jabbour, David Muller
Journal: Journal of the American College of Cardiology (2021)
WHEN A HEART TRANSPLANT IS NOT SUFFICIENT: RECURRENT GIANT CELL MYOCARDITIS
Authors: Eitan Frankel, Indranee Rajapreyar, Mahek Shah, Jesus Rame, Renee Alvarez, Jennifer Mazzoni Clifford, Justin Pelberg, Howard Massey, Vakhtang Tchantchaleishvili, Ilya Danelich, Arwa Omary, Yevgeniy Brailovsky
Journal: Journal of the American College of Cardiology (2021)
Immune profiling of COVID-19: preliminary findings and implications for the pandemic
Authors: Holden T Maecker
Journal: Journal for ImmunoTherapy of Cancer (2021)

SARS-CoV-2 infection can have widely diverse clinical outcomes, from asymptomatic infection to death, with many possible clinical symptoms and syndromes. It is thus essential to understand how the virus interacts with the host immune system to bring about these varied outcomes and to inform vaccine development. We now know that both antibody and T cell responses are induced in the majority of infected individuals, and that cross-reactive responses from other coronaviruses also exist in the uninfected population. Innate immune responses are a key focus of research and may influence the course of disease and the character of subsequent adaptive responses. Finally, baseline immune profiles and changes during early acute infection may be key to predicting the course of disease. Understanding all these aspects can help to create better immune monitoring tools for COVID-19, including tools for predicting disease severity or specific sequelae, perhaps even prior to infection.
BubR1﻿﻿ allelic effects drive phenotypic heterogeneity in mosaic-variegated aneuploidy progeria syndrome
Authors: Cynthia J. Sieben, Karthik B. Jeganathan, Grace G. Nelson, Ines Sturmlechner, Cheng Zhang, Willemijn H. van Deursen, Bjorn Bakker, Floris Foijer, Hu Li, Darren J. Baker, Jan M. van Deursen
Journal: Journal of Clinical Investigation (2020)

During the preparation of this manuscript, the same sample was inadvertently included for the +/L1002P and +/-images in Figure 2E.The
CLINICAL OUTCOMES OF P2Y12 INHIBITOR MONOTHERAPY IN PATIENTS UNDERGOING TRANSCATHETER AORTIC VALVE REPLACEMENT: LESS IS MORE!
Authors: Homam Ibrahim, Cesar Staniloae, Jorge Fuentes, Carlos Gonzalez-Lengua, Samantha Vidal, Stephanie Gaudio, Joseph Tovar, Hasan Jilaihawi, Michael Querijero, Peter Neuburger, Mathew Williams
Journal: Journal of the American College of Cardiology (2021)
Therapeutic potential of microbial modulation in pancreatic cancer
Authors: Vidhi Chandra, Florencia McAllister
Journal: Gut (2021)

Pancreatic cancer, particularly pancreatic ductal adenocarcinoma (PDAC), is an aggressive disease with a poor prognosis.1 Surgery is the only potential curative treatment, but it is only possible in patients with early-stage disease, and most patients present with non-resectable disease.1 Even in patients who undergo resection, the recurrence rate is very high due to early systemic dissemination.2 Combinatorial chemotherapy remains the standard of care for patients with advanced disease, but responses to it are heterogeneous, and its toxicity limits treatment duration.3–5 Results from clinical trials of single-agent immunotherapy have not proven its efficacy in patients with pancreatic cancer, not even when used with chemotherapy or other immunotherapeutic agents.6–8 A highly immunosuppressive tumour microenvironment (TME) has been postulated as one of the main reasons for the lack of efficacy of immunotherapy for pancreatic cancer.9–11 Therefore, novel strategies that modulate the suppressive TME are urgently needed.

The GI tract is the largest reservoir of microbes, which play important roles in modulating metabolism and immunity through interaction with host cells.12 The discovery of the association between infection with the bacterium Helicobacter pylori and the incidence of gastritis and peptic ulcer disease earned Barry Marshall and Robin Warren the Nobel Prize in Physiology or Medicine in 2005, underscoring the pivotal role of the microbiota in influencing inflammatory conditions which may predispose to cancer.13 The microbial α-diversity is a metric that quantifies the number of different species within a defined sample.14 15 In patients with many malignancies, including colorectal, breast and pancreatic cancer, the α-diversity of the gut microbiota is lower than that in healthy controls.16–18 With respect to clinical outcomes, the gut microbial α-diversity is higher in patients with melanoma that responded to immunotherapy than in those unresponsive.19 In this review, we highlight recent …
INTRAVASCULAR LITHOTRIPSY TO ENABLE VASCULAR ACCESS FOR TRANSFEMORAL TRANSCATHETER AORTIC VALVE REPLACEMENT A CASE SERIES
Authors: Diego A. Celli, Marina Byer, Camilo Gomez, Sergio Perez, Thomas Noel, Carlos Alfonso, Mauricio Cohen, Pablo Rengifo-Moreno, Eduardo De Marchena
Journal: Journal of the American College of Cardiology (2021)
CHRONIC EOSINOPHILIC LEUKEMIA: A CAUSE OF OCCULT HEART FAILURE
Authors: Muhammad Ahmed Malik, Fahd Shaukat, Sarath Lal Mannumbeth Renjithlal, Mahmood Mubasher, Vishal Tahilramani, Akbar Ahmed, Mazin Hameed
Journal: Journal of the American College of Cardiology (2021)