tbuckley/cabot-search huggingface dataset:
Infectious disease surveillance update
Authors: Rebecca Heald
Journal: The Lancet Infectious Diseases (2012)

Pregnant mothers and their babies in the UK are being immunised against pertussis after three babies died in October, which brought the number of newborn deaths from the disease since January to 13. Women 28–38 weeks pregnant are being offered the vaccine, with the aim of ensuring that their babies are born protected. 1614 pertussis infections were reported in October, which brought the number of cases since the start of the year to 7728.
Deciphering the causes of the COSMIC mutational signature 17 by combining pan-cancer data with experimental mouse models
Authors: M Tomkova, C Renard, L Urban, S Kolli, M Ardin, M Pandey, M Zhivagui, H Huskova, M Olivier, H Marusawa, B Schuster-Bockler, J Zavadil
Journal: Cancer Research (2019)
NCCN Guidelines Insights: Primary Cutaneous Lymphomas, Version 2.2020
Authors: Neha Mehta-Shah, Steven M. Horwitz, Stephen Ansell, Weiyun Z. Ai, Jeffrey Barnes, Stefan K. Barta, Mark W. Clemens, Ahmet Dogan, Kristopher Fisher, Aaron M. Goodman, Gaurav Goyal, Joan Guitart, Ahmad Halwani, Bradley M. Haverkos, Richard T. Hoppe, Eric Jacobsen, Deepa Jagadeesh, Matthew A. Lunning, Amitkumar Mehta, Elise A. Olsen, Barbara Pro, Saurabh A. Rajguru, Satish Shanbhag, Aaron Shaver, Andrei Shustov, Lubomir Sokol, Pallawi Torka, Carlos Torres-Cabala, Ryan Wilcox, Basem M. William, Jasmine Zain, Mary A. Dwyer, Hema Sundar, Youn H. Kim
Journal: Journal of the National Comprehensive Cancer Network (2020)

Mycosis fungoides (MF) is the most common subtype of cutaneous T-cell lymphoma (CTCL), and Sézary syndrome (SS) is a rare erythrodermic and leukemic subtype of CTCL characterized by significant blood involvement. Although early-stage disease can be effectively treated predominantly with skin-directed therapies, systemic therapy is often necessary for the treatment of advanced-stage disease. Systemic therapy options have evolved in recent years with the approval of novel agents such as romidepsin, brentuximab vedotin, and mogamulizumab. These NCCN Guidelines Insights discuss the diagnosis and management of MF and SS (with a focus on systemic therapy).
Severe cholestasis induced by cholic acid feeding in knockout mice of sister of P-glycoprotein
Authors: R Wang
Journal: Hepatology (2003)

Intrahepatic cholestasis is often associated with impairment of biliary bile acid secretion, a process mediated by the sister of P-glycoprotein (Spgp or Abcb11) also known as the bile salt export pump (Bsep). In humans, mutations in the Spgp gene are associated with a fatal childhood disease, type 2 progressive familial intrahepatic cholestasis (PFIC2). However in mice, the “knockout” of Spgp only results in mild cholestasis. In this study, we fed spgp−/− knockout mice with a cholic acid (CA)-supplemented diet to determine whether a more pronounced PFIC2-like phenotype could be induced. Such mice developed severe cholestasis characterized by jaundice, weight loss, elevated plasma bile acid, elevated transaminase, cholangiopathy (proliferation of bile ductules and cholangitis), liver necrosis, high mortality, and wide-ranging changes in the mRNA expression of major liver genes (16/36 examined). A surprising observation was that the bile acid output and bile flow in CA-fed mutant mice was significantly higher than anticipated. This suggests that the spgp−/− mice are able to utilize an alternative bile salt transport system. However, unlike Spgp, this system is insufficient to protect the knockout mice from cholestasis despite its high capacity. In conclusion, the spgp−/− mice provide a unique model to investigate molecular pathways associated with cholestasis and related diseases. (Hepatology 2003;38:1489-1499.)
Treatment of allergic rhinitis
Authors: Denise K C Sur, Monica L Plesa
Journal: Allergy (1994)

Allergic rhinitis is a common chronic respiratory illness that affects quality of life, productivity, and other comorbid conditions, including asthma. Treatment should be based on the patient's age and severity of symptoms. Patients should be advised to avoid known allergens and be educated about their condition. Intranasal corticosteroids are the most effective treatment and should be first-line therapy for mild to moderate disease. Moderate to severe disease not responsive to intranasal corticosteroids should be treated with second-line therapies, including antihistamines, decongestants, cromolyn, leukotriene receptor antagonists, and nonpharmacologic therapies (e.g., nasal irrigation). With the exception of cetirizine, second-generation antihistamines are less likely to cause sedation and impair performance. Immunotherapy should be considered in patients with a less than adequate response to usual treatments. Evidence does not support the use of mite-proof impermeable covers, air filtration systems, or delayed exposure to solid foods in infancy.
Infections Associated with Resterilized Pacemakers and Defibrillators
Authors: Thomas F. Khairy, Marie-Andrée Lupien, Santiago Nava, Frank Valdez Baez, Fernando Solares Ovalle, Nery E. Linarez Ochoa, Gerardo Sosa Mendoza, Cesar A. Carrazco, Christine Villemaire, Richard Cartier, Denis Roy, Mario Talajic, Marc Dubuc, Bernard Thibault, Peter G. Guerra, Lena Rivard, Katia Dyrda, Blandine Mondésert, Rafik Tadros, Julia Cadrin-Tourigny, Laurent Macle, Paul Khairy
Journal: New England Journal of Medicine (2020)

Access to pacemakers and defibrillators is problematic in places with limited resources. Resterilization and reuse of implantable cardiac devices obtained post mortem from patients in wealthier nations have been undertaken, but uncertainty around the risk of infection is a concern.A multinational program was initiated in 1983 to provide tested and resterilized pacemakers and defibrillators to underserved nations; a prospective registry was established in 2003. Patients who received reused devices in this program were matched in a 1:3 ratio with control patients who received new devices implanted in Canada. The primary outcome was infection or device-related death, with mortality from other causes modeled as a competing risk.Resterilized devices were implanted in 1051 patients (mean [±SD] age, 63.2±18.5 years; 43.6% women) in Mexico (36.0%), the Dominican Republic (28.1%), Guatemala (26.6%), and Honduras (9.3%). Overall, 85% received pacemakers and 15% received defibrillators, with one (55.5%), two (38.8%), or three (5.7%) leads. Baseline characteristics did not differ between these patients and the 3153 matched control patients. At 2 years of follow-up, infections had occurred in 21 patients (2.0%) with reused devices and in 38 (1.2%) with new devices (hazard ratio, 1.66; 95% confidence interval, 0.97 to 2.83; P = 0.06); there were no device-related deaths. The most common implicated pathogens were Staphylococcus aureus and S. epidermidis.Among patients in underserved countries who received a resterilized and reused pacemaker or defibrillator, the incidence of infection or device-related death at 2 years was 2.0%, an incidence that did not differ significantly from that seen among matched control patients with new devices in Canada.
Design and acute results of the SIMA trial
Authors: J. J. Goy, U. Kaufmann, O. Bertel, A. Gaspardone, B. Meier, A. Garachemani, M. Pieper, T. Carrel, F. Versaci, M. Hurni, M. De Benedictis, E. Eeckhout
Journal: Circulation (1998)
Senescent Stromal Cells Promote Cancer Resistance through SIRT1 Loss-Potentiated Overproduction of Small Extracellular Vesicles
Authors: Liu Han, Qilai Long, Shenjun Li, Qixia Xu, Boyi Zhang, Xuefeng Dou, Min Qian, Yannasittha Jiramongkol, Jianming Guo, Liu Cao, Y. Eugene Chin, Eric W.-F. Lam, Jing Jiang, Yu Sun
Journal: Cancer Research (2020)

Abstract Cellular senescence is a potent tumor-suppressive program that prevents neoplastic events. Paradoxically, senescent cells develop an inflammatory secretome, termed the senescence-associated secretory phenotype, which is implicated in age-related pathologies including cancer. Here, we report that senescent cells actively synthesize and release small extracellular vesicles (sEV) with a distinctive size distribution. Mechanistically, SIRT1 loss supported accelerated sEV production despite enhanced proteome-wide ubiquitination, a process correlated with ATP6V1A downregulation and defective lysosomal acidification. Once released, senescent stromal sEVs significantly altered the expression profile of recipient cancer cells and enhanced their aggressiveness, specifically drug resistance mediated by expression of ATP-binding cassette subfamily B member 4 (ABCB4). Targeting SIRT1 with agonist SRT2104 prevented development of cancer resistance by restraining sEV production by senescent stromal cells. In clinical oncology, sEVs in peripheral blood of posttreatment cancer patients were readily detectable by routine biotechniques, presenting an exploitable biomarker to monitor therapeutic efficacy and predict long-term outcome. Together, this study identifies a distinct mechanism supporting pathologic activities of senescent cells and provides a potent avenue to circumvent advanced human malignancies by cotargeting cancer cells and their surrounding microenvironment, which contributes to drug resistance via secretion of sEVs from senescent stromal cells. Significance: Senescent stromal cells produce a large number of sEVs to promote cancer resistance in therapeutic settings, a process driven by SIRT1 decline in stromal cells and ABCB4 augmentation in cancer cells. See related commentary by Wiley, p. 3193
Myocardin-Related Transcription Factors
Authors: Michael S. Parmacek
Journal: Circulation Research (2007)

The association of transcriptional coactivators with DNA-binding proteins provides an efficient mechanism to expand and modulate genetic information encoded within the genome. Myocardin-related transcription factors (MRTFs), including myocardin, MRTF-A/MKL1/MAL, and MRTF-B/MKL2, comprise a family of related transcriptional coactivators that physically associate with the MADS box transcription factor, serum response factor, and synergistically activate transcription. MRTFs transduce cytoskeletal signals to the nucleus, activating a subset of serum response factor–dependent genes promoting myogenic differentiation and cytoskeletal organization. MRTFs are multifunctional proteins that share evolutionarily conserved domains required for actin-binding, homo- and heterodimerization, high-order chromatin organization, and transcriptional activation. Mice harboring loss-of-function mutations in myocardin, MRTF-A, and MRTF-B, respectively, display distinct phenotypes, including cell autonomous defects in vascular smooth muscle cell and myoepithelial cell differentiation and function. This article reviews the molecular basis of MRTF function with particular focus on the role MRTFs play in regulating cardiovascular patterning, vascular smooth muscle cell and cardiomyocyte differentiation and in the pathogenesis of congenital heart disease and vascular proliferative syndromes.
Next-generation sequencing as an informing phenotype: A TP53 example.
Authors: Rosie O Shea, Michael P. Farrell, Roisin Clarke, Berkeley Eileen, David James Gallagher
Journal: Journal of Clinical Oncology (2015)

1554 Background: Li-Fraumeni (LFS) and Li Fraumeni like (LFL) syndromes are characterised by early onset cancers such as breast cancer, leukaemia, sarcoma, brain tumours and adrenocortical carcinoma, and are defined traditionally by clinical criteria such as Chompret and Eeles. Genetic testing for TP53 germline mutation is typically undertaken in families that satisfy these clinical criteria. Next generation sequencing and gene panel testing has resulted in more frequent TP53 testing to include families that don’t meet classic testing criteria. We investigated testing criteria and result outcome in a cohort of Irish probands undergoing TP53full sequencing. Methods: All TP53 test requests processed thought the national genetic testing laboratory between 2012 and 2014 were retrospectively reviewed. Family history data including diagnoses and age at diagnosis was ascertained through hospital charts or electronic pedigrees from two adult cancer genetic services in Ireland. Additional data including reason for testing, concordance with LFS/LFL criteria and test results were collected. Results: One hundred and thirty five TP53 test requests were identified. Family history data and test results were available on 123 of the TP53 test requests (118 female; 5 male). 74/123 (60%) didn’t meet classic LFS or LFL criteria and were TP53 mutation negative. Two individuals from this group harboured pathogenic TP53 mutations. Both were female and had a personal history of early onset bilateral breast cancer with no reported LFS cancers in the family. 49/123 (40%) met LFS or LFL criteria and were all TP53negative, apart from one female with a variant of unknown significance. 22/49 (44%) met Chompret criteria, 19/49 (38%) met Eeles and 7/49 (14%) met Eeles and Chompret and 1/49 (2%)met Classic LFS criteria. Conclusions: Stringent testing criteria miss germline mutations in TP53. Broadening the criteria for TP53 testing will redefine the clinical description of LFS and LFL, and improve our understanding of TP53 mutation expression and penetrance in this syndrome
Abstract 16150: The Impact of Annular Eccentricity and Cover Index on Paravalvular Leak After Transcatheter Aortic Valve Replacement
Authors: Anvi Raina, Mohamad Hemu, Marie-France Poulin, Clifford J Kavinsky
Journal: Circulation (2019)

Background: An eccentric annulus and a low cover index have been linked with increased paravalvular regurgitation (PVL) in transcatheter aortic valve replacement (TAVR). However, this phenomenon ha...
ERBB2/HER2 mutations are transforming and therapeutically targetable in leukemia
Authors: Sunil K. Joshi, Jamie M. Keck, Christopher A. Eide, Daniel Bottomly, Elie Traer, Jeffrey W. Tyner, Shannon K. McWeeney, Cristina E. Tognon, Brian J. Druker
Journal: Leukemia (2020)

The ErbB/HER family of receptor tyrosine kinases consists of four cell surface glycoproteins: epidermal growth factor 1 (EGFR or ErbB1), ErbB2 (c-Neu or human EGF receptor 2 [HER2]), ErbB3, and ErbB4 [1,2].Binding of the soluble ligand to its cognate ErbB receptor induces formation of homo-or heterodimer complexes, which activates receptor tyrosine kinase activity, leading to increased downstream RAS/MAPK, PI3K/AKT, and JAK/STAT signaling
601 miR-133a MEDIATES TGF-b-DEPENDENT DE-REPRESSION OF COLLAGEN-SYNTHESIS IN HEPATIC STELLATE CELLS DURING LIVER FIBROSIS
Authors: C. Roderburg, D.V. Cardenas, C. Hellerbrand, H. Zimmermann, F. Tacke, C. Trautwein, T. Luedde
Journal: Journal of Hepatology (2013)
Cardio-metabolic consequences of dietary carbohydrates: reconciling contradictions using nutritional geometry
Authors: Jibran A Wali, David Raubenheimer, Alistair M Senior, David G Le Couteur, Stephen J Simpson
Journal: Cardiovascular Research (2020)

Abstract Carbohydrates are the major source of dietary energy, but their role in health and disease remains controversial. Recent epidemiological evidence suggests that the increased consumption of carbohydrates is associated with obesity and increased risk of mortality and dietary trials show that carbohydrate restriction leads to weight loss and improved glycaemic status in obese and diabetic subjects. In contrast, the diets of populations with long and healthy lifespans (e.g. traditional Okinawans from Japan) are high in carbohydrate and low in protein, and several clinical and preclinical studies have linked low-carbohydrate–high-protein diets with increased mortality risk. In this paper we attempt to reconcile these contradictory findings by moving beyond traditional single-nutrient analyses to consider the interactions between nutrients on health outcomes. We do so using the Geometric Framework (GF), a nutritional modelling platform that explicitly considers the main and interactive effects of multiple nutrients on phenotypic characteristics. Analysis of human data by GF shows that weight loss and improved cardio-metabolic outcomes under carbohydrate restriction derive at least in part from reduced caloric intake due to the concomitantly increased proportion of protein in the diet. This is because, as in many animals, a specific appetite for protein is a major driver of food intake in humans. Conversely, dilution of protein in the diet leverages excess food intake through compensatory feeding for protein (‘protein leverage’). When protein is diluted in the diet by readily digestible carbohydrates and fats, as is the case in modern ultra-processed foods, protein leverage results in excess calorie intake, leading to rising levels of obesity and metabolic disease. However, when protein is diluted in the diet by increased quantities of less readily digestible forms of carbohydrate and fibre, energy balance is maintained and health benefits accrue, especially during middle age and early late-life. We argue that other controversies in carbohydrate research can be resolved using the GF methodology in dietary studies.
Comparative Effectiveness of Tai Chi Versus Physical Therapy for Knee Osteoarthritis
Authors: Chenchen Wang, Christopher H. Schmid, Maura D. Iversen, William F. Harvey, Roger A. Fielding, Jeffrey B. Driban, Lori Lyn Price, John B. Wong, Kieran F. Reid, Ramel Rones, Timothy McAlindon
Journal: Annals of Internal Medicine (2016)

Studies of patients with osteoarthritis have found improved outcomes with Tai Chi, a traditional Chinese mind–body practice, compared with usual physical activity, wait-list, or attention control g...
Convolutional neural networks for classification of Alzheimer's disease: Overview and reproducible evaluation
Authors: Junhao Wen, Elina Thibeau-Sutre, Mauricio Diaz-Melo, Jorge Samper-González, Alexandre Routier, Simona Bottani, Didier Dormont, Stanley Durrleman, Ninon Burgos, Olivier Colliot
Journal: Medical Image Analysis (2020)
In Vivo Assessment of Size-Selective Glomerular Sieving in Transplanted Human Induced Pluripotent Stem Cell–Derived Kidney Organoids
Authors: Cathelijne W. van den Berg, Angela Koudijs, Laila Ritsma, Ton J. Rabelink
Journal: Journal of the American Society of Nephrology (2020)

The utility of kidney organoids in regenerative medicine will rely on the functionality of the glomerular and tubular structures in these tissues. Recent studies have demonstrated the vascularization and subsequent maturation of human pluripotent stem cell-derived kidney organoids after renal subcapsular transplantation. This raises the question of whether the glomeruli also become functional upon transplantation.We transplanted kidney organoids under the renal capsule of the left kidney in immunodeficient mice followed by the implantation of a titanium imaging window on top of the kidney organoid. To assess glomerular function in the transplanted human pluripotent stem cell-derived kidney tissue 1, 2, and 3 weeks after transplantation, we applied high-resolution intravital multiphoton imaging through the imaging window during intravenous infusion of fluorescently labeled low and high molecular mass dextran molecules or albumin.After vascularization, glomerular structures in the organoid displayed dextran and albumin size selectivity across their glomerular filtration barrier. We also observed evidence of proximal tubular dextran reuptake.Our results demonstrate that human pluripotent stem cell-derived glomeruli can develop an appropriate barrier function and discriminate between molecules of varying size. These characteristics together with tubular presence of low molecular mass dextran provide clear evidence of functional filtration. This approach to visualizing glomerular filtration function will be instrumental for translation of organoid technology for clinical applications as well as for disease modeling.
Abstract 15430: More Frequent Remote Home Monitoring Decreases Blood Pressure in an Unselected Population of People With Diabetes
Authors: Karen Xu, Roberta James, Wei Lu, Anoop Sangha, Bimal R Shah
Journal: Circulation (2019)

Introduction: A meta-analysis by Bray (2010) showed home blood pressure monitoring (HBPM) modestly improves hypertension (HTN) control compared to usual care (systolic -3.82 mmHg [95% CI -5.61, -2....
Overuse of Diagnostic Brain Imaging Among Patients With Stage IA Non–Small Cell Lung Cancer
Authors: Michael G. Milligan, Angel M. Cronin, Yolonda Colson, Kenneth Kehl, Debra N. Yeboa, Deborah Schrag, Aileen B. Chen
Journal: Journal of the National Comprehensive Cancer Network (2020)

Background: Among patients diagnosed with stage IA non–small cell lung cancer (NSCLC), the incidence of occult brain metastasis is low, and several professional societies recommend against brain imaging for staging purposes. The goal of this study was to characterize the use of brain imaging among Medicare patients diagnosed with stage IA NSCLC. Methods: Using data from linked SEER-Medicare claims, we identified patients diagnosed with AJCC 8th edition stage IA NSCLC in 2004 through 2013. Patients were classified as having received brain imaging if they underwent head CT or brain MRI from 1 month before to 3 months after diagnosis. We identified factors associated with receipt of brain imaging using multivariable logistic regression. Results: Among 13,809 patients with stage IA NSCLC, 3,417 (25%) underwent brain imaging at time of diagnosis. The rate of brain imaging increased over time, from 23.5% in 2004 to 28.7% in 2013 ( P =.0006). There was significant variation in the use of brain imaging across hospital service areas, with rates ranging from 0% to 64.0%. Factors associated with a greater likelihood of brain imaging included older age (odds ratios [ORs] of 1.16 for 70–74 years, 1.13 for 75–79 years, 1.31 for 80–84 years, and 1.46 for ≥85 years compared with 65–69 years; all P &lt;.05), female sex (OR, 1.09; P &lt;.05), black race (OR 1.23; P &lt;.05), larger tumor size (ORs of 1.23 for 11–20 mm and 1.28 for 21–30 mm tumors vs 1–10 mm tumors; all P &lt;.05), and higher modified Charlson-Deyo comorbidity score (OR, 1.28 for score &gt;1 vs score of 0; P &lt;.05). Conclusions: Roughly 1 in 4 patients with stage IA NSCLC received brain imaging at the time of diagnosis despite national recommendations against the practice. Although several patient factors are associated with receipt of brain imaging, there is significant geographic variation across the United States. Closer adherence to clinical guidelines is likely to result in more cost-effective care.