tbuckley/cabot-search huggingface dataset:
Growth Hormone Replacement Delays the Progression of Chronic Heart Failure Combined With Growth Hormone Deficiency
Authors: Antonio Cittadini, Alberto M Marra, Michele Arcopinto, Emanuele Bobbio, Andrea Salzano, Domenico Sirico, Raffaele Napoli, Annamaria Colao, Salvatore Longobardi, Ragavendra R Baliga, Eduardo Bossone, Luigi Saccà
Journal: JACC Heart Failure (2013)
Changing behaviour: an essential component of tackling health inequalities
Authors: Theresa M Marteau, Harry Rutter, Michael Marmot
Journal: BMJ (2021)

Life expectancy in England is stalling, while at the same time health inequalities are widening.The 2020 Marmot review of health inequalities in England showed that between 2010 and 2018 the gap in life expectancy at birth between those living in the least and most deprived areas increased. 1 For men the gap increased from 9.1 to 9.5 years and for women from 6.8 to 7.7 years.The time people spend in poor health has also increased across England since 2010, from 15.8 to 16.2 years for men, and 18.7 to 19.4 years for women.But these average figures mask an even steeper social gradient than that seen for life expectancy, meaning that those in more deprived areas spend a larger proportion of their already shorter lives in poor health.
Free 25(Oh)D Is Higher in Adult Patients with Type 1 Diabetes Mellitus Compared to Healthy Individuals
Authors: Alexandra Povaliaeva, Ekaterina Pigarova, Artem Zhukov, Viktor Bogdanov, Larisa Dzeranova, Olga Mel’nikova, Elena Pekareva, Natalya Malysheva, Vitaliy Ioutsi, Larisa Nikankina, Liudmila Rozhinskaya
Journal: Metabolism (2021)
Menin is necessary for long term maintenance of meningioma-1 driven leukemia
Authors: Clara Libbrecht, Hongbo M. Xie, Molly C. Kingsley, Jessica N. Haladyna, Simone S. Riedel, Fatemeh Alikarami, Alexandra Lenard, Gerard M. McGeehan, Patricia Ernst, Kathrin M. Bernt
Journal: Leukemia (2021)

Abstract Translocations of Meningioma-1 (MN1) occur in a subset of acute myeloid leukemias (AML) and result in high expression of MN1, either as a full-length protein, or as a fusion protein that includes most of the N-terminus of MN1. High levels of MN1 correlate with poor prognosis. When overexpressed in murine hematopoietic progenitors, MN1 causes an aggressive AML characterized by an aberrant myeloid precursor-like gene expression program that shares features of KMT2A -rearranged ( KMT2A -r) leukemia, including high levels of Hoxa and Meis1 gene expression. Compounds that target a critical KMT2A–Menin interaction have proven effective in KMT2A -r leukemia. Here, we demonstrate that Menin ( Men1 ) is also critical for the self-renewal of MN1-driven AML through the maintenance of a distinct gene expression program. Genetic inactivation of Men1 led to a decrease in the number of functional leukemia-initiating cells. Pharmacologic inhibition of the KMT2A–Menin interaction decreased colony-forming activity, induced differentiation programs in MN1-driven murine leukemia and decreased leukemic burden in a human AML xenograft carrying an MN1-ETV6 translocation. Collectively, these results nominate Menin inhibition as a promising therapeutic strategy in MN1-driven leukemia.
Retinal applications of swept source optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA)
Authors: Inês Laíns, Jay C. Wang, Ying Cui, Raviv Katz, Filippos Vingopoulos, Giovanni Staurenghi, Demetrios G. Vavvas, Joan W. Miller, John B. Miller
Journal: Progress in Retinal and Eye Research (2021)
Pruritus, Sleep, and Productivity: A Post Hoc Analysis of Abrocitinib Versus Placebo in Patients With Moderate-to-Severe Atopic Dermatitis (AD) From JADE MONO-2
Authors: Gil Yosipovitch, Luz Fonacier, Sonja Ständer, John Su, Melinda Gooderham, Jacek Szepietowski, Mette Deleuran, Giampiero Girolomoni, Pinaki Biswas, Claire Feeney, Hernan Valdez, Ricardo Rojo, Andrew Thorpe, Gary Chan, Joseph Cappelleri, Marco DiBonaventura, Daniela Myers
Journal: Journal of Allergy and Clinical Immunology (2021)
Optimising pyrazinamide for the treatment of tuberculosis
Authors: Nan Zhang, Radojka M. Savic, Martin J. Boeree, Charles A. Peloquin, Marc Weiner, Norbert Heinrich, Erin Bliven-Sizemore, Patrick P.J. Phillips, Michael Hoelscher, William Whitworth, Glenn Morlock, James Posey, Jason E. Stout, William Mac Kenzie, Robert Aarnoutse, Kelly E. Dooley
Journal: European Respiratory Journal (2021)

Pyrazinamide is a potent sterilising agent that shortens the treatment duration needed to cure tuberculosis. It is synergistic with novel and existing drugs for tuberculosis. The dose of pyrazinamide that optimises efficacy while remaining safe is uncertain, as is its potential role in shortening treatment duration further. Pharmacokinetic data, sputum culture, and safety laboratory results were compiled from Tuberculosis Trials Consortium (TBTC) studies 27 and 28 and Pan-African Consortium for the Evaluation of Antituberculosis Antibiotics (PanACEA) multi-arm multi-stage tuberculosis (MAMS-TB), multi-centre phase 2 trials in which participants received rifampicin (range 10–35 mg·kg −1 ), pyrazinamide (range 20–30 mg·kg −1 ), plus two companion drugs. Pyrazinamide pharmacokinetic–pharmacodynamic (PK–PD) and pharmacokinetic-toxicity analyses were performed. In TBTC studies (n=77), higher pyrazinamide maximum concentration (C max ) was associated with shorter time to culture conversion (TTCC) and higher probability of 2-month culture conversion (p-value&lt;0.001). Parametric survival analyses showed that relationships varied geographically, with steeper PK–PD relationships seen among non-African than African participants. In PanACEA MAMS-TB (n=363), TTCC decreased as pyrazinamide C max increased and varied by rifampicin area under the curve (p-value&lt;0.01). Modelling and simulation suggested that very high doses of pyrazinamide (&gt;4500 mg) or increasing both pyrazinamide and rifampicin would be required to reach targets associated with treatment shortening. Combining all trials, liver toxicity was rare (3.9% with grade 3 or higher liver function tests (LFT)), and no relationship was seen between pyrazinamide C max and LFT levels. Pyrazinamide's microbiological efficacy increases with increasing drug concentrations. Optimising pyrazinamide alone, though, is unlikely to be sufficient to allow tuberculosis treatment shortening; rather, rifampicin dose would need to be increased in parallel.
Early Environmental Upheaval and the Risk for Schizophrenia
Authors: Vincent Paquin, Mylène Lapierre, Franz Veru, Suzanne King
Journal: Annual Review of Clinical Psychology (2021)

Why does prenatal exposure to wars, natural disasters, urbanicity, or winter increase the risk for schizophrenia? Research from the last two decades has provided rich insight about the underlying chains of causation at play during environmental upheaval, from conception to early infancy. In this review, we appraise the evidence linking schizophrenia spectrum disorder to prenatal maternal stress, obstetric complications, early infections, and maternal nutrition and other lifestyle factors. We discuss putative mechanisms, including the maternal stress system, perinatal hypoxia, and maternal-offspring immune activation. We propose that gene-environment interactions, timing during development, and sex differentiate the neuropsychiatric outcomes. Future research should pursue the translation of animal studies to humans and the longitudinal associations between early exposures, intermediate phenotypes, and psychiatric disorders. Finally, to paint a comprehensive model of risk and to harness targets for prevention, we argue that risk factors should be situated within the individual's personal ecosystem.
Radiation Dose De-Escalation in HPV-Positive Oropharynx Cancer: When Will It Be an Acceptable Standard of Care?
Authors: Anupama Chundury, Sung Kim
Journal: Journal of Clinical Oncology (2021)

Human papillomavirus (HPV) is now the most common cause of oropharyngeal squamous cell carcinoma (OPSCC) in the United States, with recent data suggesting that for every two new HPV-negative diagnoses of OPSCC, there are five new HPV-positive ones. 1 Observational studies and subset analyses of several prospective trials have demonstrated that patients with HPV-positive OPSCC present at a younger age and have a better overall prognosis when compared with HPV-negative patients. 2,3Although definitive chemoradiation therapy (CRT) for HPVpositive OPSCC is often curative, the resultant acute and long-term toxicity can significantly affect patients' quality of life. 4As such, there is now a strong push toward treatment de-escalation or deintensification for these patients, with the goal of reducing toxicity without affecting cure rates.
Comparison and correlation of commercial SARS-CoV-2 real-time-PCR assays, Ireland, June 2020
Authors: Anne Carroll, Eleanor McNamara
Journal: Eurosurveillance (2021)

We report the performance of a variety of commercially available SARS-CoV-2 PCR kits, used in several different sites across Ireland to determine if Ct values across platforms are comparable. We also investigate whether a Ct value, a surrogate for calculated viral loads in the absence of viral culture of > 34 can be used to exclude SARS-CoV-2 infection and its complications. We found a variation in Ct values from different assays for the same calculated viral load; this should be taken into consideration for result interpretation.
CircNR3C2 promotes HRD1-mediated tumor-suppressive effect via sponging miR-513a-3p in triple-negative breast cancer
Authors: Ya Fan, Jia Wang, Wen Jin, Yifei Sun, Yuemei Xu, Yipin Wang, Xiubin Liang, Dongming Su
Journal: Molecular Cancer (2021)

Abstract Background E3 ubiquitin ligase HRD1 (HMG-CoA reductase degradation protein 1, alias synoviolin with SYVN1 as the official gene symbol) was found downregulated and acting as a tumor suppressor in breast cancer, while the exact expression profile of HRD1 in different breast cancer subtypes remains unknown. Recent studies characterized circular RNAs (circRNAs) playing an regulatory role as miRNA sponge in tumor progression, presenting a new viewpoint for the post-transcriptional regulation of cancer-related genes. Methods Examination of the expression of HRD1 protein and mRNA was implemented using public microarray/RNA-sequencing datasets and breast cancer tissues/cell lines. Based on public RNA-sequencing results, online databases and enrichment/clustering analyses were used to predict the specific combinations of circRNA/miRNA that potentially govern HRD1 expression. Gain-of-function and rescue experiments in vitro and in vivo were executed to evaluate the suppressive effects of circNR3C2 on breast cancer progression through HRD1-mediated proteasomal degradation of Vimentin, which was identified using immunoblotting, immunoprecipitation, and in vitro ubiquitination assays. Results HRD1 is significantly underexpressed in triple-negative breast cancer (TNBC) against other subtypes and has an inverse correlation with Vimentin, inhibiting the proliferation, migration, invasion and EMT (epithelial-mesenchymal transition) process of breast cancer cells via inducing polyubiquitination-mediated proteasomal degradation of Vimentin. CircNR3C2 (hsa_circ_0071127) is also remarkably downregulated in TNBC, negatively correlated with the distant metastasis and lethality of invasive breast carcinoma. Overexpressing circNR3C2 in vitro and in vivo leads to a crucial enhancement of the tumor-suppressive effects of HRD1 through sponging miR-513a-3p. Conclusions Collectively, we elucidated a bona fide circNR3C2/miR-513a-3p/HRD1/Vimentin axis that negatively regulates the metastasis of TNBC, suggesting that circNR3C2 and HRD1 can act as potential prognostic biomarkers. Our study may facilitate the development of therapeutic agents targeting circNR3C2 and HRD1 for patients with aggressive breast cancer.
Long‐Term Outcomes in Patients With Connective Tissue Disease–Associated Pulmonary Arterial Hypertension in the Modern Treatment Era: Meta‐Analyses of Randomized, Controlled Trials and Observational Registries
Authors: Dinesh Khanna, Carol Zhao, Rajan Saggar, Stephen C. Mathai, Lorinda Chung, J. Gerry Coghlan, Mehul Shah, John Hartney, Vallerie McLaughlin
Journal: Arthritis & Rheumatology (2021)

Objective Data on the magnitude of benefit of modern therapies for pulmonary arterial hypertension (PAH) in connective tissue disease (CTD)–associated PAH are limited. In this study, we performed meta‐analyses of randomized, controlled trials (RCTs) and registries to quantify the benefit of these modern therapies in patients with CTD‐PAH. Methods The PubMed and Embase databases were searched for articles reporting data from RCTs or registries published between January 1, 2000 and November 25, 2019. Eligibility criteria included multicenter studies with ≥30 CTD‐PAH patients. For an RCT to be included, the trial had to evaluate an approved PAH therapy, and long‐term risks of clinical morbidity and mortality or 6‐minute walk distance had to be reported. For a registry to be included, survival rates had to be reported. Random‐effects models were used to pool the data. Results Eleven RCTs (total of 4,329 patients; 1,267 with CTD‐PAH) and 19 registries (total of 9,739 patients; 4,008 with CTD‐PAH) were included. Investigational therapy resulted in a 36% reduction in the risk of clinical morbidity/mortality events both in the overall PAH population (hazard ratio [HR] 0.64, 95% confidence interval [95% CI] 0.54, 0.75; P &lt; 0.001) and in CTD‐PAH patients (HR 0.64, 95% CI 0.51, 0.81; P &lt; 0.001) as compared to control subjects. The survival rate was lower in CTD‐PAH patients compared to all PAH patients (survival rate 62%, 95% CI 57, 67% versus 72%, 95% CI 69, 75% at 3 years). The survival rate in CTD‐PAH patients treated primarily after 2010 was higher than that in CTD‐PAH patients treated before 2010 (survival rate 73%, 95% CI 62, 81% versus 65%, 95% CI 59, 71% at 3 years). Conclusion Modern therapy provides a similar reduction in morbidity/mortality risk in patients with CTD‐PAH when compared to the PAH population overall. Risk of death is higher in CTD‐PAH patients than in those with PAH overall, but survival has improved in the last 10 years, which may be related to increased screening and/or new treatment approaches. Early detection of PAH in patients with CTD and up‐front intensive treatment are warranted.
PD-1H (VISTA) Induces Immune Evasion in Acute Myeloid Leukemia
Authors: Tae Kon Kim, Xue Han, Jun Wang, Miguel Sanmamed, Tianxiang Zhang, Stephanie Halene, Manoj M Pillai, Jun Lu, Mina Xu, Amer M. Zeidan, Steven D. Gore, Madhav Dhodapkar, Lieping Chen
Journal: Blood (2017)
5′-tRF-GlyGCC: a tRNA-derived small RNA as a novel biomarker for colorectal cancer diagnosis
Authors: Yingmin Wu, Xiangling Yang, Guanmin Jiang, Haisheng Zhang, Lichen Ge, Feng Chen, Jiexin Li, Huanliang Liu, Hongsheng Wang
Journal: Genome Medicine (2021)

Abstract Background tRNA-derived small RNAs (tDRs), which are widely distributed in human tissues including blood and urine, play an important role in the progression of cancer. However, the expression of tDRs in colorectal cancer (CRC) plasma and their potential diagnostic values have not been systematically explored. Methods The expression profiles of tDRs in plasma of CRC and health controls (HCs) are investigated by small RNA sequencing. The level and diagnostic value of 5′-tRF-GlyGCC are evaluated by quantitative PCR in plasma samples from 105 CRC patients and 90 HCs. The mechanisms responsible for biogenesis of 5′-tRF-GlyGCC are checked by in vitro and in vivo models. Results 5′-tRF-GlyGCC is dramatically increased in plasma of CRC patients compared to that of HCs. The area under curve (AUC) for 5′-tRF-GlyGCC in CRC group is 0.882. The combination of carcinoembryonic antigen (CEA) and carbohydrate antigen 199 (CA199) with 5′-tRF-GlyGCC improves the AUC to 0.926. Consistently, the expression levels of 5′-tRF-GlyGCC in CRC cells and xenograft tissues are significantly greater than that in their corresponding controls. Blood cells co-cultured with CRC cells or mice xenografted with CRC tumors show increased levels of 5′-tRF-GlyGCC. In addition, we find that the increased expression of 5′-tRF-GlyGCC is dependent on the upregulation of AlkB homolog 3 (ALKBH3), a tRNA demethylase which can promote tRNA cleaving to generate tDRs. Conclusions The level of 5′-tRF-GlyGCC in plasma is a promising diagnostic biomarker for CRC diagnosis.
Consensus recommendations for MRI and PET imaging of primary central nervous system lymphoma: guideline statement from the International Primary CNS Lymphoma Collaborative Group (IPCG)
Authors: Ramon F Barajas, Letterio S Politi, Nicoletta Anzalone, Heiko Schöder, Christopher P Fox, Jerrold L Boxerman, Timothy J Kaufmann, C Chad Quarles, Benjamin M Ellingson, Dorothee Auer, Ovidiu C Andronesi, Andres J M Ferreri, Maciej M Mrugala, Christian Grommes, Edward A Neuwelt, Prakash Ambady, James L Rubenstein, Gerald Illerhaus, Motoo Nagane, Tracy T Batchelor, Leland S Hu
Journal: Neuro-Oncology (2021)

Advanced molecular and pathophysiologic characterization of primary central nervous system lymphoma (PCNSL) has revealed insights into promising targeted therapeutic approaches. Medical imaging plays a fundamental role in PCNSL diagnosis, staging, and response assessment. Institutional imaging variation and inconsistent clinical trial reporting diminishes the reliability and reproducibility of clinical response assessment. In this context, we aimed to: (1) critically review the use of advanced positron emission tomography (PET) and magnetic resonance imaging (MRI) in the setting of PCNSL; (2) provide results from an international survey of clinical sites describing the current practices for routine and advanced imaging, and (3) provide biologically based recommendations from the International PCNSL Collaborative Group (IPCG) on adaptation of standardized imaging practices. The IPCG provides PET and MRI consensus recommendations built upon previous recommendations for standardized brain tumor imaging protocols (BTIP) in primary and metastatic disease. A biologically integrated approach is provided to addresses the unique challenges associated with the imaging assessment of PCNSL. Detailed imaging parameters facilitate the adoption of these recommendations by researchers and clinicians. To enhance clinical feasibility, we have developed both "ideal" and "minimum standard" protocols at 3T and 1.5T MR systems that will facilitate widespread adoption.
Abstract 15618: Cardiac Microstructural Abnormalities Confer Differential Effects on Heart Failure Risk by Sex
Authors: Emmanuella Demosthenes, Gerran Salto, Ewa Osypiuk, Plamen Stantchev, Elizabeth H Kim, Pranoti Hiremath, Susan Cheng
Journal: Circulation (2019)

Background: Incremental alterations in the orientation and integrity of myocardial fibers can be assessed using advanced ultrasonic image analysis. The ability to detect such microstructural abnorm...
A Text-Book of Anatomy and Physiology.
Journal: JAMA (1929)

This attractively bound and beautifully illustrated volume on anatomy and physiology is designed primarily for the use of students in training schools for nurses where the two subjects are given as a combined course. It follows the approved plans as regards the sequence and proportion of the various divisions of these subjects. Each chapter is followed by a list of review questions, and at the end of the book there is a helpful glossary and an index. Attempts to present these subjects to beginners are beset with difficulties which should induce occasional soul searching by medical writers. An example is the section on leukocytes on page 327, where the authors undertake to explain the differential count. This is an impossible task and will be, as long as hematologists adhere to their present illogical vocabulary. On page 526 the authors use the words urination and micturition interchangeably, as do many medical
Pathological response and survival with neoadjuvant therapy in melanoma: a pooled analysis from the International Neoadjuvant Melanoma Consortium (INMC)
Authors: Alexander M. Menzies, Rodabe N. Amaria, Elisa A. Rozeman, Alexander C. Huang, Michael T. Tetzlaff, Bart A. van de Wiel, Serigne Lo, Ahmad A. Tarhini, Elizabeth M. Burton, Thomas E. Pennington, Robyn P. M. Saw, Xiaowei Xu, Giorgos C. Karakousis, Paolo A. Ascierto, Andrew J. Spillane, Alexander C. J. van Akkooi, Michael A. Davies, Tara C. Mitchell, Hussein A. Tawbi, Richard A. Scolyer, Jennifer A. Wargo, Christian U. Blank, Georgina V. Long
Journal: Nature Medicine (2021)
Percutaneous endoscopic sigmoidopexy: a simple procedure within every endoscopistʼs reach
Authors: Marco Alburquerque Miranda, Miquel Gomez Artacho, Alba Vargas García, Gemma García Continente, Cesar Ledezma Frontado, Montserrat Figa Francesch, Ferrán González-Huix Lladó
Journal: Endoscopy (2021)

An 87-year-old man with severe co-morbidities (obstructive pulmonary disease and chronic heart failure, among others) and chronic constipation had previous admissions to the hospital six episodes of large-bowel obstruction, including four documented sigmoid volvuli, and two others that were directly treated with placement of a decompression tube. In the year after the emergency endoscopic detorsion, there were ten more episodes. Surgery was ruled out because of his high risk, and the patient underwent percutaneous endoscopic sigmoidopexy ([Video 1]).
To a Firstborn Son
Authors: Scott Hendrik Van Hoeven
Journal: JAMA (2021)

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A modified vaccinia Ankara vector-based vaccine protects macaques from SARS-CoV-2 infection, immune pathology, and dysfunction in the lungs
Authors: Nanda Kishore Routhu, Narayanaiah Cheedarla, Sailaja Gangadhara, Venkata Satish Bollimpelli, Arun K. Boddapati, Ayalnesh Shiferaw, Sheikh Abdul Rahman, Anusmita Sahoo, Venkata Viswanadh Edara, Lilin Lai, Katharine Floyd, Shelly Wang, Stephanie Fischinger, Caroline Atyeo, Sally A. Shin, Sanjeev Gumber, Shannon Kirejczyk, Joyce Cohen, Sherrie M. Jean, Jennifer S. Wood, Fawn Connor-Stroud, Rachelle L. Stammen, Amit A. Upadhyay, Kathryn Pellegrini, David Montefiori, Pei-Yong Shi, Vineet D. Menachery, Galit Alter, Thomas H. Vanderford, Steven E. Bosinger, Mehul S. Suthar, Rama Rao Amara
Journal: Immunity (2021)