The Role of the EGF Receptor in Sex Differences in Kidney Injury.

1 month ago
Related Articles

The Role of the EGF Receptor in Sex Differences in Kidney Injury.

J Am Soc Nephrol. 2019 09;30(9):1659-1673

Authors: Zhang MZ, Sasaki K, Li Y, Li Z, Pan Y, Jin GN, Wang Y, Niu A, Wang S, Fan X, Chen JC, Borza C, Yang H, Pozzi A, Fogo AB, Harris RC

Abstract
BACKGROUND: Sex differences mediating predisposition to kidney injury are well known, with evidence indicating lower CKD incidence rates and slower decline in renal function in nondiabetic CKD for premenopausal women compared with men. However, signaling pathways involved have not been elucidated to date. The EGF receptor (EGFR) is widely expressed in the kidney in glomeruli and tubules, and persistent and dysregulated EGFR activation mediates progressive renal injury.
METHODS: To investigate the sex differences in response to renal injury, we examined EGFR expression in mice, in human kidney tissue, and in cultured cell lines.
RESULTS: In wild type mice, renal mRNA and protein EGFR levels were comparable in males and females at postnatal day 7 but were significantly lower in age-matched adult females than in adult males. Similar gender differences in renal EGFR expression were detected in normal adult human kidneys. In Dsk5 mutant mice with a gain-of-function allele that increases basal EGFR kinase activity, males had progressive glomerulopathy, albuminuria, loss of podocytes, and tubulointerstitial fibrosis, but female Dsk5 mice had minimal kidney injury. Oophorectomy had no effect on renal EGFR levels in female Dsk5 mice, while castration protected against the kidney injury in male Dsk5 mice, in association with a reduction in EGFR expression to levels seen in females. Conversely, testosterone increased EGFR expression and renal injury in female Dsk5 mice. Testosterone directly stimulated EGFR expression in cultured kidney cells.
CONCLUSIONS: These studies indicate that differential renal EGFR expression plays a role in the sex differences in susceptibility to progressive kidney injury that may be mediated at least in part by testosterone.

PMID: 31292196 [PubMed - indexed for MEDLINE]

The Extracellular Matrix Receptor Discoidin Domain Receptor 1 Regulates Collagen Transcription by Translocating to the Nucleus.

1 month ago
Related Articles

The Extracellular Matrix Receptor Discoidin Domain Receptor 1 Regulates Collagen Transcription by Translocating to the Nucleus.

J Am Soc Nephrol. 2019 09;30(9):1605-1624

Authors: Chiusa M, Hu W, Liao HJ, Su Y, Borza CM, de Caestecker MP, Skrypnyk NI, Fogo AB, Pedchenko V, Li X, Zhang MZ, Hudson BG, Basak T, Vanacore RM, Zent R, Pozzi A

Abstract
BACKGROUND: The discoidin domain receptor 1 (DDR1) is activated by collagens, upregulated in injured and fibrotic kidneys, and contributes to fibrosis by regulating extracellular matrix production, but how DDR1 controls fibrosis is poorly understood. DDR1 is a receptor tyrosine kinase (RTK). RTKs can translocate to the nucleus via a nuclear localization sequence (NLS) present on the receptor itself or a ligand it is bound to. In the nucleus, RTKs regulate gene expression by binding chromatin directly or by interacting with transcription factors.
METHODS: To determine whether DDR1 translocates to the nucleus and whether this event is mediated by collagen-induced DDR1 activation, we generated renal cells expressing wild-type or mutant forms of DDR1 no longer able to bind collagen. Then, we determined the location of the DDR1 upon collagen stimulation. Using both biochemical assays and immunofluorescence, we analyzed the steps involved in DDR1 nuclear translocation.
RESULTS: We show that although DDR1 and its natural ligand, collagen, lack an NLS, DDR1 is present in the nucleus of injured human and mouse kidney proximal tubules. We show that DDR1 nuclear translocation requires collagen-mediated receptor activation and interaction of DDR1 with SEC61B, a component of the Sec61 translocon, and nonmuscle myosin IIA and β-actin. Once in the nucleus, DDR1 binds to chromatin to increase the transcription of collagen IV, a major collagen upregulated in fibrosis.
CONCLUSIONS: These findings reveal a novel mechanism whereby activated DDR1 translates to the nucleus to regulate synthesis of profibrotic molecules.

PMID: 31383731 [PubMed - indexed for MEDLINE]

Autism-linked dopamine transporter mutation alters striatal dopamine neurotransmission and dopamine-dependent behaviors.

1 month 1 week ago
Related Articles

Autism-linked dopamine transporter mutation alters striatal dopamine neurotransmission and dopamine-dependent behaviors.

J Clin Invest. 2019 05 16;129(8):3407-3419

Authors: DiCarlo GE, Aguilar JI, Matthies HJ, Harrison FE, Bundschuh KE, West A, Hashemi P, Herborg F, Rickhag M, Chen H, Gether U, Wallace MT, Galli A

Abstract
The precise regulation of synaptic dopamine (DA) content by the dopamine transporter (DAT) ensures the phasic nature of the DA signal, which underlies the ability of DA to encode reward prediction error, thereby driving motivation, attention, and behavioral learning. Disruptions to the DA system are implicated in a number of neuropsychiatric disorders, including attention deficit hyperactivity disorder (ADHD) and, more recently, Autism Spectrum Disorder (ASD). An ASD-associated de novo mutation in the SLC6A3 gene resulting in a threonine to methionine substitution at site 356 (DAT T356M) was recently identified and has been shown to drive persistent reverse transport of DA (i.e. anomalous DA efflux) in transfected cells and to drive hyperlocomotion in Drosophila melanogaster. A corresponding mutation in the leucine transporter, a DAT-homologous transporter, promotes an outward-facing transporter conformation upon substrate binding, a conformation possibly underlying anomalous dopamine efflux. Here we investigated in vivo the impact of this ASD-associated mutation on DA signaling and ASD-associated behaviors. We found that mice homozygous for this mutation display impaired striatal DA neurotransmission and altered DA-dependent behaviors that correspond with some of the behavioral phenotypes observed in ASD.

PMID: 31094705 [PubMed - indexed for MEDLINE]

Cross-reactivity between vancomycin, teicoplanin and telavancin in HLA-A*32:01 positive vancomycin DRESS patients sharing an HLA-Class II haplotype.

1 month 1 week ago
Related Articles

Cross-reactivity between vancomycin, teicoplanin and telavancin in HLA-A*32:01 positive vancomycin DRESS patients sharing an HLA-Class II haplotype.

J Allergy Clin Immunol. 2020 May 18;:

Authors: Nakkam N, Gibson A, Mouhtouris E, Konvinse K, Holmes N, Chua KY, Deshpande P, Li D, Ostrov DA, Trubiano J, Phillips EJ

Abstract
CAPSULE SUMMARY: All fifteen patients with HLA-A*32:01 restricted vancomycin-induced DRESS, showed negative ex vivo responses to dalbavancin however two showed cross-reactivity to teicoplanin and telavancin. Adjunctive diagnostic testing should be considered to detect potential cross-reactivity amongst glycopeptides.

PMID: 32439433 [PubMed - as supplied by publisher]

Social determinants of health and survival in humans and other animals.

1 month 1 week ago
Related Articles

Social determinants of health and survival in humans and other animals.

Science. 2020 May 22;368(6493):

Authors: Snyder-Mackler N, Burger JR, Gaydosh L, Belsky DW, Noppert GA, Campos FA, Bartolomucci A, Yang YC, Aiello AE, O'Rand A, Harris KM, Shively CA, Alberts SC, Tung J

Abstract
The social environment, both in early life and adulthood, is one of the strongest predictors of morbidity and mortality risk in humans. Evidence from long-term studies of other social mammals indicates that this relationship is similar across many species. In addition, experimental studies show that social interactions can causally alter animal physiology, disease risk, and life span itself. These findings highlight the importance of the social environment to health and mortality as well as Darwinian fitness-outcomes of interest to social scientists and biologists alike. They thus emphasize the utility of cross-species analysis for understanding the predictors of, and mechanisms underlying, social gradients in health.

PMID: 32439765 [PubMed - in process]

Cardiovascular Toxicities Associated with Hydroxychloroquine and Azithromycin: An Analysis of the World Health Organization Pharmacovigilance Database.

1 month 1 week ago
Related Articles

Cardiovascular Toxicities Associated with Hydroxychloroquine and Azithromycin: An Analysis of the World Health Organization Pharmacovigilance Database.

Circulation. 2020 May 22;:

Authors: Nguyen LS, Dolladille C, Drici MD, Fenioux C, Alexandre J, Mira JP, Moslehi JJ, Roden DM, Funck-Brentano C, Salem JE

PMID: 32442023 [PubMed - as supplied by publisher]

Blood Pressure Management in Afferent Baroreflex Failure: JACC Review Topic of the Week.

1 month 1 week ago
Related Articles

Blood Pressure Management in Afferent Baroreflex Failure: JACC Review Topic of the Week.

J Am Coll Cardiol. 2019 12 10;74(23):2939-2947

Authors: Biaggioni I, Shibao CA, Diedrich A, Muldowney JAS, Laffer CL, Jordan J

Abstract
Afferent baroreflex failure is most often due to damage of the carotid sinus nerve because of neck surgery or radiation. The clinical picture is characterized by extreme blood pressure lability with severe hypertensive crises, hypotensive episodes, and orthostatic hypotension, making it the most difficult form of hypertension to manage. There is little evidence-based data to guide treatment. Recommendations rely on understanding the underlying pathophysiology, relevant clinical pharmacology, and anecdotal experience. The goal of treatment should be improving quality of life rather than normalization of blood pressure, which is rarely achievable. Long-acting central sympatholytic drugs are the mainstay of treatment, used at the lowest doses that prevent the largest hypertensive surges. Short-acting clonidine should be avoided because of rebound hypertension, but can be added to control residual hypertensive episodes, often triggered by mental stress or exertion. Hypotensive episodes can be managed with countermeasures and short-acting pressor agents if necessary.

PMID: 31806138 [PubMed - indexed for MEDLINE]

Gut-Proglucagon-Derived Peptides Are Essential for Regulating Glucose Homeostasis in Mice.

1 month 1 week ago
Related Articles

Gut-Proglucagon-Derived Peptides Are Essential for Regulating Glucose Homeostasis in Mice.

Cell Metab. 2019 11 05;30(5):976-986.e3

Authors: Song Y, Koehler JA, Baggio LL, Powers AC, Sandoval DA, Drucker DJ

Abstract
The importance of pancreatic versus intestinal-derived GLP-1 for glucose homeostasis is controversial. We detected active GLP-1 in the mouse and human pancreas, albeit at extremely low levels relative to glucagon. Accordingly, to elucidate the metabolic importance of intestinal proglucagon-derived peptides (PGDPs), we generated mice with reduction of Gcg expression within the distal (GcgDistalGut-/-) or entire (GcgGut-/-) gut. Substantial reduction of gut Gcg expression markedly reduced circulating levels of GLP-1, and impaired glucose homeostasis, associated with increased levels of GIP, and accelerated gastric emptying. GcgDistalGut-/- mice similarly exhibited lower circulating GLP-1 and impaired oral glucose tolerance. Nevertheless, plasma levels of insulin remained normal following glucose administration in the absence of gut-derived GLP-1. Collectively, our findings identify the essential importance of gut-derived PGDPs for maintaining levels of circulating GLP-1, control of gastric emptying, and glucose homeostasis.

PMID: 31495689 [PubMed - indexed for MEDLINE]

Transethnic Genome-Wide Association Study Provides Insights in the Genetic Architecture and Heritability of Long QT Syndrome.

1 month 1 week ago

Transethnic Genome-Wide Association Study Provides Insights in the Genetic Architecture and Heritability of Long QT Syndrome.

Circulation. 2020 May 20;:

Authors: Lahrouchi N, Tadros R, Crotti L, Mizusawa Y, Postema PG, Beekman L, Walsh R, Hasegawa K, Barc J, Ernsting M, Turkowski KL, Mazzanti A, Beckmann BM, Shimamoto K, Diamant UB, Wijeyeratne YD, Kucho Y, Robyns T, Ishikawa T, Arbelo E, Christiansen M, Winbo A, Jabbari R, Lubitz SA, Steinfurt J, Rudic B, Loeys B, Shoemaker MB, Weeke PE, Pfeiffer R, Davies B, Andorin A, Hofman N, Dagradi F, Pedrazzini M, Tester DJ, Bos JM, Sarquella-Brugada G, Campuzano Ó, Platonov PG, Stallmeyer B, Zumhagen S, Nannenberg EA, Veldink JH, van den Berg LH, Al-Chalabi A, Shaw CE, Shaw PJ, Morrison KE, Andersen PM, Müller-Nurasyid M, Cusi D, Barlassina C, Galan P, Lathrop M, Munter M, Werge T, Ribasés M, Aung T, Khor CC, Ozaki M, Lichtner P, Meitinger T, van Tintelen JP, Hoedemaekers Y, Denjoy I, Leenhardt A, Napolitano C, Shimizu W, Schott JJ, Gourraud JB, Makiyama T, Ohno S, Itoh H, Krahn AD, Antzelevitch C, Roden DM, Saenen J, Borggrefe M, Odening KE, Ellinor PT, Tfelt-Hansen J, Skinner JR, van den Berg MP, Olesen MS, Brugada J, Brugada R, Makita N, Breckpot J, Yoshinaga M, Behr ER, Rydberg A, Aiba T, Kääb S, Priori SG, Guicheney P, Tan HL, Newton-Cheh C, Ackerman MJ, Schwartz PJ, Schulze-Bahr E, Probst V, Horie M, Wilde AA, Tanck MWT, Bezzina CR

Abstract
Background: Long QT syndrome (LQTS) is a rare genetic disorder and a major preventable cause of sudden cardiac death in the young. A causal rare genetic variant with large effect size is identified in up to 80% of probands (genotype positive) and cascade family screening shows incomplete penetrance of genetic variants. Furthermore, a proportion of cases meeting diagnostic criteria for LQTS remain genetically elusive despite genetic testing of established genes (genotype negative). These observations raise the possibility that common genetic variants with small effect size contribute to the clinical picture of LQTS. This study aimed to characterize and quantify the contribution of common genetic variation to LQTS disease susceptibility. Methods: We conducted genome-wide association studies (GWAS) followed by transethnic meta-analysis in 1,656 unrelated LQTS patients of European or Japanese ancestry and 9,890 controls to identify susceptibility single nucleotide polymorphisms (SNPs). We estimated the SNP heritability (h2SNP) of LQTS and tested the genetic correlation between LQTS susceptibility and other cardiac traits. Furthermore, we tested the aggregate effect of the 68 SNPs previously associated with QTc in the general population using a polygenic risk score (PRSQT). Results: Genome-wide association analysis identified three loci associated with LQTS at genome-wide statistical significance (P<5x10-8) near NOS1AP, KCNQ1 and KLF12, and one missense variant in KCNE1 (p.Asp85Asn) at the suggestive threshold (P<10-6). Heritability analyses showed that ~15% of variance in overall LQTS susceptibility was attributable to common genetic variation (h2SNP 0.148; standard error [SE] 0.019). LQTS susceptibility showed a strong genome-wide genetic correlation with the QT interval in the general population (rg=0.40, P=3.2x10-3). PRSQT was greater in LQTS cases compared to controls (P<10-13), and notably, among LQTS patients PRSQT was greater in genotype negative compared to genotype positive patients (P<0.005). Conclusions: This work establishes an important role for common genetic variation in susceptibility to LQTS. We demonstrate overlap between genetic control of the QT interval in the general population and genetic factors contributing to LQTS susceptibility. Using polygenic risk score analyses aggregating common genetic variants that modulate the QT interval in the general population, we provide evidence for a polygenic architecture in genotype negative LQTS.

PMID: 32429735 [PubMed - as supplied by publisher]

Dose-Adjusted EPOCH-R Compared With R-CHOP as Frontline Therapy for Diffuse Large B-Cell Lymphoma: Clinical Outcomes of the Phase III Intergroup Trial Alliance/CALGB 50303.

1 month 2 weeks ago
Related Articles

Dose-Adjusted EPOCH-R Compared With R-CHOP as Frontline Therapy for Diffuse Large B-Cell Lymphoma: Clinical Outcomes of the Phase III Intergroup Trial Alliance/CALGB 50303.

J Clin Oncol. 2019 07 20;37(21):1790-1799

Authors: Bartlett NL, Wilson WH, Jung SH, Hsi ED, Maurer MJ, Pederson LD, Polley MC, Pitcher BN, Cheson BD, Kahl BS, Friedberg JW, Staudt LM, Wagner-Johnston ND, Blum KA, Abramson JS, Reddy NM, Winter JN, Chang JE, Gopal AK, Chadburn A, Mathew S, Fisher RI, Richards KL, Schöder H, Zelenetz AD, Leonard JP

Abstract
PURPOSE: Alliance/CALGB 50303 (NCT00118209), an intergroup, phase III study, compared dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R) with standard rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) as frontline therapy for diffuse large B-cell lymphoma.
PATIENTS AND METHODS: Patients received six cycles of DA-EPOCH-R or R-CHOP. The primary objective was progression-free survival (PFS); secondary clinical objectives included response rate, overall survival (OS), and safety.
RESULTS: Between 2005 and 2013, 524 patients were registered; 491 eligible patients were included in the final analysis. Most patients (74%) had stage III or IV disease; International Prognostic Index (IPI) risk groups included 26% IPI 0 to 1, 37% IPI 2, 25% IPI 3, and 12% IPI 4 to 5. At a median follow-up of 5 years, PFS was not statistically different between the arms (hazard ratio, 0.93; 95% CI, 0.68 to 1.27; P = .65), with a 2-year PFS rate of 78.9% (95% CI, 73.8% to 84.2%) for DA-EPOCH-R and 75.5% (95% CI, 70.2% to 81.1%) for R-CHOP. OS was not different (hazard ratio, 1.09; 95% CI, 0.75 to 1.59; P = .64), with a 2-year OS rate of 86.5% (95% CI, 82.3% to 91%) for DA-EPOCH-R and 85.7% (95% CI, 81.4% to 90.2%) for R-CHOP. Grade 3 and 4 adverse events were more common (P < .001) in the DA-EPOCH-R arm than the R-CHOP arm, including infection (16.9% v 10.7%, respectively), febrile neutropenia (35.0% v 17.7%, respectively), mucositis (8.4% v 2.1%, respectively), and neuropathy (18.6% v 3.3%, respectively). Five treatment-related deaths (2.1%) occurred in each arm.
CONCLUSION: In the 50303 study population, the more intensive, infusional DA-EPOCH-R was more toxic and did not improve PFS or OS compared with R-CHOP. The more favorable results with R-CHOP compared with historical controls suggest a potential patient selection bias and may preclude generalizability of results to specific risk subgroups.

PMID: 30939090 [PubMed - indexed for MEDLINE]

Cardiovascular Toxicities Associated With Ibrutinib.

1 month 2 weeks ago
Related Articles

Cardiovascular Toxicities Associated With Ibrutinib.

J Am Coll Cardiol. 2019 10 01;74(13):1667-1678

Authors: Salem JE, Manouchehri A, Bretagne M, Lebrun-Vignes B, Groarke JD, Johnson DB, Yang T, Reddy NM, Funck-Brentano C, Brown JR, Roden DM, Moslehi JJ

Abstract
BACKGROUND: Ibrutinib has revolutionized treatment for several B-cell malignancies. However, a recent clinical trial where ibrutinib was used in a front-line setting showed increased mortality during treatment compared with conventional chemotherapy. Cardiovascular toxicities were suspected as the culprit but not directly assessed in the study.
OBJECTIVES: The purpose of this study was to identify and characterize cardiovascular adverse drug reactions (CV-ADR) associated with ibrutinib.
METHODS: This study utilized VigiBase (International pharmacovigilance database) and performed a disproportionality analysis using reporting odds ratios (ROR) and information component (IC) to determine whether CV-ADR and CV-ADR deaths were associated with ibrutinib. IC compares observed and expected values to find associations between drugs and adverse drug reactions using disproportionate Bayesian-reporting; IC025 (lower end of the IC 95% credibility interval) >0 is significant.
RESULTS: This study identified 303 ibrutinib-associated cardiovascular deaths. Ibrutinib was associated with higher reporting of supraventricular arrhythmias (SVAs) (ROR: 23.1; 95% confidence interval: 21.6 to 24.7; p < 0.0001; IC025: 3.97), central nervous system (CNS) hemorrhagic events (ROR: 3.7; 95% confidence interval: 3.4 to 4.1; p < 0.0001; IC025: 1.63), heart failure (ROR: 3.5; 95% confidence interval: 3.1 to 3.8; p < 0.0001; IC025: 1.46), ventricular arrhythmias (ROR: 4.7; 95% confidence interval: 3.7 to 5.9; p < 0.0001; IC025: 0.96), conduction disorders (ROR: 3.5; 95% confidence interval: 2.7 to 4.6; p < 0.0001; IC025: 0.76), CNS ischemic events (ROR: 2.2; 95% confidence interval: 2.0 to 2.5; p < 0.0001; IC025: 0.73), and hypertension (ROR: 1.7; 95% confidence interval: 1.5 to 1.9; p < 0.0001; IC025: 0.4). CV-ADR often occurred early after ibrutinib administration. Importantly, CV-ADR were associated with fatalities that ranged from ∼10% (SVAs and ventricular arrhythmias) to ∼20% (CNS events, heart failure, and conduction disorders). Ibrutinib-associated SVA portends poor prognosis when CNS events occur concomitantly, with 28.8% deaths (15 of 52 cases).
CONCLUSIONS: Severe and occasionally fatal cardiac events occur in patients exposed to ibrutinib. These events should be considered in patient care and in clinical trial designs. (Evaluation of Reporting of Cardio-vascular Adverse Events With Antineoplastic and Immunomodulating Agents [EROCA]; NCT03530215).

PMID: 31558250 [PubMed - indexed for MEDLINE]

Genome-wide association study identifies 32 novel breast cancer susceptibility loci from overall and subtype-specific analyses.

1 month 2 weeks ago
Related Articles

Genome-wide association study identifies 32 novel breast cancer susceptibility loci from overall and subtype-specific analyses.

Nat Genet. 2020 May 18;:

Authors: Zhang H, Ahearn TU, Lecarpentier J, Barnes D, Beesley J, Qi G, Jiang X, O'Mara TA, Zhao N, Bolla MK, Dunning AM, Dennis J, Wang Q, Ful ZA, Aittomäki K, Andrulis IL, Anton-Culver H, Arndt V, Aronson KJ, Arun BK, Auer PL, Azzollini J, Barrowdale D, Becher H, Beckmann MW, Behrens S, Benitez J, Bermisheva M, Bialkowska K, Blanco A, Blomqvist C, Bogdanova NV, Bojesen SE, Bonanni B, Bondavalli D, Borg A, Brauch H, Brenner H, Briceno I, Broeks A, Brucker SY, Brüning T, Burwinkel B, Buys SS, Byers H, Caldés T, Caligo MA, Calvello M, Campa D, Castelao JE, Chang-Claude J, Chanock SJ, Christiaens M, Christiansen H, Chung WK, Claes KBM, Clarke CL, Cornelissen S, Couch FJ, Cox A, Cross SS, Czene K, Daly MB, Devilee P, Diez O, Domchek SM, Dörk T, Dwek M, Eccles DM, Ekici AB, Evans DG, Fasching PA, Figueroa J, Foretova L, Fostira F, Friedman E, Frost D, Gago-Dominguez M, Gapstur SM, Garber J, García-Sáenz JA, Gaudet MM, Gayther SA, Giles GG, Godwin AK, Goldberg MS, Goldgar DE, González-Neira A, Greene MH, Gronwald J, Guénel P, Häberle L, Hahnen E, Haiman CA, Hake CR, Hall P, Hamann U, Harkness EF, Heemskerk-Gerritsen BAM, Hillemanns P, Hogervorst FBL, Holleczek B, Hollestelle A, Hooning MJ, Hoover RN, Hopper JL, Howell A, Huebner H, Hulick PJ, Imyanitov EN, kConFab Investigators, ABCTB Investigators, Isaacs C, Izatt L, Jager A, Jakimovska M, Jakubowska A, James P, Janavicius R, Janni W, John EM, Jones ME, Jung A, Kaaks R, Kapoor PM, Karlan BY, Keeman R, Khan S, Khusnutdinova E, Kitahara CM, Ko YD, Konstantopoulou I, Koppert LB, Koutros S, Kristensen VN, Laenkholm AV, Lambrechts D, Larsson SC, Laurent-Puig P, Lazaro C, Lazarova E, Lejbkowicz F, Leslie G, Lesueur F, Lindblom A, Lissowska J, Lo WY, Loud JT, Lubinski J, Lukomska A, MacInnis RJ, Mannermaa A, Manoochehri M, Manoukian S, Margolin S, Martinez ME, Matricardi L, McGuffog L, McLean C, Mebirouk N, Meindl A, Menon U, Miller A, Mingazheva E, Montagna M, Mulligan AM, Mulot C, Muranen TA, Nathanson KL, Neuhausen SL, Nevanlinna H, Neven P, Newman WG, Nielsen FC, Nikitina-Zake L, Nodora J, Offit K, Olah E, Olopade OI, Olsson H, Orr N, Papi L, Papp J, Park-Simon TW, Parsons MT, Peissel B, Peixoto A, Peshkin B, Peterlongo P, Peto J, Phillips KA, Piedmonte M, Plaseska-Karanfilska D, Prajzendanc K, Prentice R, Prokofyeva D, Rack B, Radice P, Ramus SJ, Rantala J, Rashid MU, Rennert G, Rennert HS, Risch HA, Romero A, Rookus MA, Rübner M, Rüdiger T, Saloustros E, Sampson S, Sandler DP, Sawyer EJ, Scheuner MT, Schmutzler RK, Schneeweiss A, Schoemaker MJ, Schöttker B, Schürmann P, Senter L, Sharma P, Sherman ME, Shu XO, Singer CF, Smichkoska S, Soucy P, Southey MC, Spinelli JJ, Stone J, Stoppa-Lyonnet D, EMBRACE Study, GEMO Study Collaborators, Swerdlow AJ, Szabo CI, Tamimi RM, Tapper WJ, Taylor JA, Teixeira MR, Terry M, Thomassen M, Thull DL, Tischkowitz M, Toland AE, Tollenaar RAEM, Tomlinson I, Torres D, Troester MA, Truong T, Tung N, Untch M, Vachon CM, van den Ouweland AMW, van der Kolk LE, van Veen EM, vanRensburg EJ, Vega A, Wappenschmidt B, Weinberg CR, Weitzel JN, Wildiers H, Winqvist R, Wolk A, Yang XR, Yannoukakos D, Zheng W, Zorn KK, Milne RL, Kraft P, Simard J, Pharoah PDP, Michailidou K, Antoniou AC, Schmidt MK, Chenevix-Trench G, Easton DF, Chatterjee N, García-Closas M

Abstract
Breast cancer susceptibility variants frequently show heterogeneity in associations by tumor subtype1-3. To identify novel loci, we performed a genome-wide association study including 133,384 breast cancer cases and 113,789 controls, plus 18,908 BRCA1 mutation carriers (9,414 with breast cancer) of European ancestry, using both standard and novel methodologies that account for underlying tumor heterogeneity by estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status and tumor grade. We identified 32 novel susceptibility loci (P < 5.0 × 10-8), 15 of which showed evidence for associations with at least one tumor feature (false discovery rate < 0.05). Five loci showed associations (P < 0.05) in opposite directions between luminal and non-luminal subtypes. In silico analyses showed that these five loci contained cell-specific enhancers that differed between normal luminal and basal mammary cells. The genetic correlations between five intrinsic-like subtypes ranged from 0.35 to 0.80. The proportion of genome-wide chip heritability explained by all known susceptibility loci was 54.2% for luminal A-like disease and 37.6% for triple-negative disease. The odds ratios of polygenic risk scores, which included 330 variants, for the highest 1% of quantiles compared with middle quantiles were 5.63 and 3.02 for luminal A-like and triple-negative disease, respectively. These findings provide an improved understanding of genetic predisposition to breast cancer subtypes and will inform the development of subtype-specific polygenic risk scores.

PMID: 32424353 [PubMed - as supplied by publisher]

TERAVOLT: Thoracic Cancers International COVID-19 Collaboration.

1 month 2 weeks ago

TERAVOLT: Thoracic Cancers International COVID-19 Collaboration.

Cancer Cell. 2020 May 16;:

Authors: Whisenant JG, Trama A, Torri V, De Toma A, Viscardi G, Cortellini A, Micheilin O, Barlesi F, Dingemans AC, Van Meerbeeck J, Pancaldi V, Soo RA, Leighl NB, Peters S, Wakelee H, Garassino MC, Horn L

Abstract
Prior publications on small subsets of cancer patients infected with SARS CoV-2 have shown an increased risk of mortality compared to the general population. Furthermore, patients with thoracic malignancies are thought to be at particularly high risk given their older age, smoking habits, and pre-existing cardio-pulmonary comorbidities. For this reason, physicians around the world have formed TERAVOLT, a global consortium dedicated to understanding the impact of COVID-19 on patients with thoracic malignancies.

PMID: 32425702 [PubMed - as supplied by publisher]

HLA-A*32:01 is strongly associated with vancomycin-induced drug reaction with eosinophilia and systemic symptoms.

1 month 2 weeks ago
Related Articles

HLA-A*32:01 is strongly associated with vancomycin-induced drug reaction with eosinophilia and systemic symptoms.

J Allergy Clin Immunol. 2019 07;144(1):183-192

Authors: Konvinse KC, Trubiano JA, Pavlos R, James I, Shaffer CM, Bejan CA, Schutte RJ, Ostrov DA, Pilkinton MA, Rosenbach M, Zwerner JP, Williams KB, Bourke J, Martinez P, Rwandamuriye F, Chopra A, Watson M, Redwood AJ, White KD, Mallal SA, Phillips EJ

Abstract
BACKGROUND: Vancomycin is a prevalent cause of the severe hypersensitivity syndrome drug reaction with eosinophilia and systemic symptoms (DRESS), which leads to significant morbidity and mortality and commonly occurs in the setting of combination antibiotic therapy, affecting future treatment choices. Variations in HLA class I in particular have been associated with serious T cell-mediated adverse drug reactions, which has led to preventive screening strategies for some drugs.
OBJECTIVE: We sought to determine whether variation in the HLA region is associated with vancomycin-induced DRESS.
METHODS: Probable vancomycin-induced DRESS cases were matched 1:2 with tolerant control subjects based on sex, race, and age by using BioVU, Vanderbilt's deidentified electronic health record database. Associations between DRESS and carriage of HLA class I and II alleles were assessed by means of conditional logistic regression. An extended sample set from BioVU was used to conduct a time-to-event analysis of those exposed to vancomycin with and without the identified HLA risk allele.
RESULTS: Twenty-three subjects met the inclusion criteria for vancomycin-associated DRESS. Nineteen (82.6%) of 23 cases carried HLA-A*32:01 compared with 0 (0%) of 46 of the matched vancomycin-tolerant control subjects (P = 1 × 10-8) and 6.3% of the BioVU population (n = 54,249, P = 2 × 10-16). Time-to-event analysis of DRESS development during vancomycin treatment among the HLA-A*32:01-positive group indicated that 19.2% had DRESS and did so within 4 weeks.
CONCLUSIONS: HLA-A*32:01 is strongly associated with vancomycin-induced DRESS in a population of predominantly European ancestry. HLA-A*32:01 testing could improve antibiotic safety, help implicate vancomycin as the causal drug, and preserve future treatment options with coadministered antibiotics.

PMID: 30776417 [PubMed - indexed for MEDLINE]

Microvascular Disease, Peripheral Artery Disease, and Amputation.

1 month 2 weeks ago
Related Articles

Microvascular Disease, Peripheral Artery Disease, and Amputation.

Circulation. 2019 08 06;140(6):449-458

Authors: Beckman JA, Duncan MS, Damrauer SM, Wells QS, Barnett JV, Wasserman DH, Bedimo RJ, Butt AA, Marconi VC, Sico JJ, Tindle HA, Bonaca MP, Aday AW, Freiberg MS

Abstract
BACKGROUND: The mechanism of adverse limb events associated with peripheral artery disease remains incompletely understood. We investigated whether microvascular disease is associated with amputation in a large cohort of veterans to determine whether microvascular disease diagnosed in any location increases the risk of amputation alone and in concert with peripheral artery disease.
METHODS: Participants in the Veterans Aging Cohort Study were recruited from April 1, 2003 through December 31, 2014. We excluded participants with known prior lower limb amputation. Using time-updated Cox proportional hazards regression, we analyzed the effect of prevalent microvascular disease (retinopathy, neuropathy, and nephropathy) and peripheral artery disease status on the risk of incident amputation events after adjusting for demographics and cardiovascular risk factors.
RESULTS: Among 125 674 veterans without evidence of prior amputation at baseline, the rate of incident amputation over a median of 9.3 years of follow-up was 1.16 per 1000 person-years, yielding a total of 1185 amputations. In time-updated multivariable-adjusted analyses, compared with those without peripheral artery disease or microvascular disease, microvascular disease alone was associated with a 3.7-fold (95% CI, 3.0-4.6) increased risk of amputation; peripheral artery disease alone conferred a 13.9-fold (95% CI, 11.3-17.1) elevated risk of amputation; and the combination of peripheral artery disease and microvascular disease was associated with a 22.7-fold (95% CI, 18.3-28.1) increased risk of amputation.
CONCLUSIONS: Independent of traditional risk factors, the presence of microvascular disease increases the risk of amputation alone and synergistically increases risk in patients with peripheral artery disease. Further research is needed to understand the mechanisms by which this occurs.

PMID: 31280589 [PubMed - indexed for MEDLINE]

SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues.

1 month 2 weeks ago

SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues.

Cell. 2020 Apr 27;:

Authors: Ziegler CGK, Allon SJ, Nyquist SK, Mbano IM, Miao VN, Tzouanas CN, Cao Y, Yousif AS, Bals J, Hauser BM, Feldman J, Muus C, Wadsworth MH, Kazer SW, Hughes TK, Doran B, Gatter GJ, Vukovic M, Taliaferro F, Mead BE, Guo Z, Wang JP, Gras D, Plaisant M, Ansari M, Angelidis I, Adler H, Sucre JMS, Taylor CJ, Lin B, Waghray A, Mitsialis V, Dwyer DF, Buchheit KM, Boyce JA, Barrett NA, Laidlaw TM, Carroll SL, Colonna L, Tkachev V, Peterson CW, Yu A, Zheng HB, Gideon HP, Winchell CG, Lin PL, Bingle CD, Snapper SB, Kropski JA, Theis FJ, Schiller HB, Zaragosi LE, Barbry P, Leslie A, Kiem HP, Flynn JL, Fortune SM, Berger B, Finberg RW, Kean LS, Garber M, Schmidt AG, Lingwood D, Shalek AK, Ordovas-Montanes J, HCA Lung Biological Network. Electronic address: lung-network@humancellatlas.org, HCA Lung Biological Network

Abstract
There is pressing urgency to understand the pathogenesis of the severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV-2), which causes the disease COVID-19. SARS-CoV-2 spike (S) protein binds angiotensin-converting enzyme 2 (ACE2), and in concert with host proteases, principally transmembrane serine protease 2 (TMPRSS2), promotes cellular entry. The cell subsets targeted by SARS-CoV-2 in host tissues and the factors that regulate ACE2 expression remain unknown. Here, we leverage human, non-human primate, and mouse single-cell RNA-sequencing (scRNA-seq) datasets across health and disease to uncover putative targets of SARS-CoV-2 among tissue-resident cell subsets. We identify ACE2 and TMPRSS2 co-expressing cells within lung type II pneumocytes, ileal absorptive enterocytes, and nasal goblet secretory cells. Strikingly, we discovered that ACE2 is a human interferon-stimulated gene (ISG) in vitro using airway epithelial cells and extend our findings to in vivo viral infections. Our data suggest that SARS-CoV-2 could exploit species-specific interferon-driven upregulation of ACE2, a tissue-protective mediator during lung injury, to enhance infection.

PMID: 32413319 [PubMed - as supplied by publisher]

Ectonucleoside Triphosphate Diphosphohydrolase-3 Antibody Targets Adult Human Pancreatic β Cells for In Vitro and In Vivo Analysis.

1 month 3 weeks ago
Related Articles

Ectonucleoside Triphosphate Diphosphohydrolase-3 Antibody Targets Adult Human Pancreatic β Cells for In Vitro and In Vivo Analysis.

Cell Metab. 2019 03 05;29(3):745-754.e4

Authors: Saunders DC, Brissova M, Phillips N, Shrestha S, Walker JT, Aramandla R, Poffenberger G, Flaherty DK, Weller KP, Pelletier J, Cooper T, Goff MT, Virostko J, Shostak A, Dean ED, Greiner DL, Shultz LD, Prasad N, Levy SE, Carnahan RH, Dai C, Sévigny J, Powers AC

Abstract
Identification of cell-surface markers specific to human pancreatic β cells would allow in vivo analysis and imaging. Here we introduce a biomarker, ectonucleoside triphosphate diphosphohydrolase-3 (NTPDase3), that is expressed on the cell surface of essentially all adult human β cells, including those from individuals with type 1 or type 2 diabetes. NTPDase3 is expressed dynamically during postnatal human pancreas development, appearing first in acinar cells at birth, but several months later its expression declines in acinar cells while concurrently emerging in islet β cells. Given its specificity and membrane localization, we utilized an NTPDase3 antibody for purification of live human β cells as confirmed by transcriptional profiling, and, in addition, for in vivo imaging of transplanted human β cells. Thus, NTPDase3 is a cell-surface biomarker of adult human β cells, and the antibody directed to this protein should be a useful new reagent for β cell sorting, in vivo imaging, and targeting.

PMID: 30449685 [PubMed - indexed for MEDLINE]

Multiplexed In Situ Imaging Mass Cytometry Analysis of the Human Endocrine Pancreas and Immune System in Type 1 Diabetes.

1 month 3 weeks ago
Related Articles

Multiplexed In Situ Imaging Mass Cytometry Analysis of the Human Endocrine Pancreas and Immune System in Type 1 Diabetes.

Cell Metab. 2019 03 05;29(3):769-783.e4

Authors: Wang YJ, Traum D, Schug J, Gao L, Liu C, HPAP Consortium, Atkinson MA, Powers AC, Feldman MD, Naji A, Chang KM, Kaestner KH

Abstract
The interaction between the immune system and endocrine cells in the pancreas is crucial for the initiation and progression of type 1 diabetes (T1D). Imaging mass cytometry (IMC) enables multiplexed assessment of the abundance and localization of more than 30 proteins on the same tissue section at 1-μm resolution. Herein, we have developed a panel of 33 antibodies that allows for the quantification of key cell types including pancreatic exocrine cells, islet cells, immune cells, and stromal components. We employed this panel to analyze 12 pancreata obtained from donors with clinically diagnosed T1D and 6 pancreata from non-diabetic controls. In the pancreata from donors with T1D, we simultaneously visualized significant alterations in islet architecture, endocrine cell composition, and immune cell presentation. Indeed, we demonstrate the utility of IMC to investigate complex events on the cellular level that will provide new insights on the pathophysiology of T1D.

PMID: 30713110 [PubMed - indexed for MEDLINE]

Checked
2 hours 51 minutes ago
Recent Discoveries
NCBI: db=pubmed; Term=(((Abbate MJ[Author] OR Abdel-Kader K[Author] OR Abdolrasulnia R[Author] OR Abraham RL[Author] OR Abramson VG[Author] OR Abu-Halimah AJ[Author] OR Adam-Eldien R[Author] OR Adkins KD[Author] OR "Ahmad, Firdos"[Author] OR Algood H[Author] OR Allocco CS[Author] OR Allos BM[Author] OR Ancell KK[Author] OR Anderson BC[Author] OR Anderson RW[Author] OR Angel FB[Author] OR Annapureddy N[Author] OR Annis K[Author] OR Aronoff DM[Author] OR Arteaga CL[Author] OR Aslam M[Author] OR Atwater KK[Author] OR Aune TM[Author] OR Awad JA[Author] OR Babaev VR[Author] OR Bachmann JM[Author] OR Bachmann K[Author] OR Bader DM[Author] OR Bagai J[Author] OR Baker AL[Author] OR Baker MT[Author] OR Balko JM[Author] OR Bao S[Author] OR Barnado AL[Author] OR Basher S[Author] OR Bastarache JA[Author] OR Baum HB[Author] OR Beard MH[Author] OR Beaulieu DB[Author] OR Becker JR[Author] OR Beckman J[Author] OR Beeghly-Fadiel A[Author] OR Bell SP[Author] OR Berlin JD[Author] OR Bernard GR[Author] OR Bhave G[Author] OR Biaggioni I[Author] OR Birchmore DA[Author] OR Birdee GS[Author] OR Birdwell KA[Author] OR Bischoff L[Author] OR Blackwell TS[Author] OR Bledsoe-Frazee J[Author] OR Blind R[Author] OR Bloch KC[Author] OR Blot WJ[Author] OR Bonami RH[Author] OR Boone JM[Author] OR Borza C[Author] OR Bowman B[Author] OR Bowton EA[Author] OR Boyd AS[Author] OR Bradham WS[Author] OR Bradshaw EA[Author] OR Brady DW[Author] OR Brandt SJ[Author] OR Brantley-Sieders DM[Author] OR Breyer RM[Author] OR Brissova M[Author] OR Brittain EL[Author] OR Brooks CR[Author] OR Brown AW[Author] OR Brown JD[Author] OR Brown KL[Author] OR Brown NJ[Author] OR Brummel NE[Author] OR Brunwasser S[Author] OR Buchowski MS[Author] OR Budko S[Author] OR Bulus NM[Author] OR Burgner A[Author] OR Burgos EB[Author] OR Burke J[Author] OR Butka BJ[Author] OR Byers JD[Author] OR Byram BR[Author] OR Byram J[Author] OR Byrd BF[Author] OR Byrne M[Author] OR "Cai, Hui"[Author] OR "Cai, Quiyan"[Author] OR "Cai, Ying"[Author] OR Campbell IS[Author] OR Campbell WB[Author] OR "Cao, Zheng"[Author] OR Cardin DB[Author] OR Backlund DC[Author] OR Carranza Leon B[Author] OR Carrier EJ[Author] OR "Case, Jane"[Author] OR Castellanos E[Author] OR Castilho JL[Author] OR Cavanaugh KL[Author] OR Chakkalakal RJ[Author] OR Chambers MR[Author] OR Champion R[Author] OR "Chan, Emily"[Author] OR Chapman RL[Author] OR Chastain CA[Author] OR "Chen, Jin"[Author] OR Chen JC[Author] OR "Chen, Wei"[Author] OR "Cheng Huifang"[Author] OR Chestnut MH[Author] OR Chidsey G[Author] OR Chinratanalab SD[Author] OR Chinratanalab W[Author] OR Chism D[Author] OR Choma NN[Author] OR Christman BW[Author] OR Chun YW[Author] OR Chung CP[Author] OR Chung CY[Author] OR Chung-Hussain H[Author] OR Churchill LR[Author] OR Churchwell AL[Author] OR Clagett A[Author] OR Clair WK[Author] OR Clayton AS[Author] OR Cleator JH[Author] OR "Cleek, John"[Author] OR Clement LE[Author] OR Cleveland CM[Author] OR Clouse K[Author] OR Coburn LA[Author] OR Coffey RJ[Author] OR Collins O[Author] OR Colvin K[Author] OR Concepcion BP[Author] OR Copeland BH[Author] OR Cornell RF[Author] OR Cover TL[Author] OR Cox NJ[Author] OR Craddock LS[Author] OR Craig KS[Author] OR Craven DM[Author] OR Crenshaw MH[Author] OR Crofford LJ[Author] OR Crossley GH[Author] OR Culp JA[Author] OR Currier KA[Author] OR Dahir KM[Author] OR "Dai, Chunhua"[Author] OR "Dai, Qi"[Author] OR Damp JB[Author] OR Daniels TL[Author] OR Dantzler DM[Author] OR Das SR[Author] OR Davidson SR[Author] OR Davis LK[Author] OR deCaestecker MP[Author] OR DeLozier JS[Author] OR Dennis K[Author] OR DeSio C[Author] OR Devin JK[Author] OR Didier IA[Author] OR Diedrich AM[Author] OR Dikalov S[Author] OR Dikalova A[Author] OR Dittus RS[Author] OR Dixon JH[Author] OR Dole N[Author] OR Dorris SE[Author] OR Douglas GC[Author] OR Drake WP[Author] OR Drake-Davis DJ[Author] OR Dugan LL[Author] OR Duggan M[Author] OR Duley CV[Author] OR Dunn GD[Author] OR Dworski RT[Author] OR Dwyer JP[Author] OR Edwards NE[Author] OR Edwards TL[Author] OR Eguakun KA[Author] OR Elasy TA[Author] OR Elias BC[Author] OR Ellis CD[Author] OR Ellis CR[Author] OR Ellis DL[Author] OR Ellis SE[Author] OR El-Sourady MH[Author] OR Ely EW[Author] OR Engelhardt BG[Author] OR English CS[Author] OR Epplein M[Author] OR Epstein PA[Author] OR Estrada JC[Author] OR Fahrenholz J[Author] OR Fanning JB[Author] OR Feng Q[Author] OR Feoktistov IA[Author] OR Ferguson JF[Author] OR Ferrell B[Author] OR Ferrell NJ[Author] OR Fessel JP[Author] OR Ficken SL[Author] OR Fife H[Author] OR Fine JD[Author] OR Fischer MA[Author] OR Fiske CT[Author] OR Fiske WH[Author] OR Fissell R[Author] OR Fissell WH[Author] OR Flemmons KD[Author] OR Flemmons LN[Author] OR Fong PP[Author] OR Force TL[Author] OR Fortman KD[Author] OR Fowke JH[Author] OR Fowler MJ[Author] OR Franklin JL[Author] OR Franklin JM[Author] OR Fredi JL[Author] OR Freiberg MS[Author] OR Friesinger III GC[Author] OR Frischhertz BP[Author] OR Fuchs HA[Author] OR Gaddy JA[Author] OR Gainer JV[Author] OR Galindo CL[Author] OR Galloway MM[Author] OR Gamboa A[Author] OR Gamboa AM[Author] OR Gamboa JL[Author] OR Gannon MA[Author] OR Gant RA[Author] OR Garland EM[Author] OR Garrett A[Author] OR Gaudieri S[Author] OR Georgostathis D[Author] OR Gewin LS[Author] OR Gilbert J[Author] OR Girard TD[Author] OR Glazer MD[Author] OR Gobert AP[Author] OR Goebel LW[Author] OR Goff LA[Author] OR Williams LA[Author] OR Golper TA[Author] OR Gomez JA[Author] OR Goodman SA[Author] OR Gore JE[Author] OR Gould E[Author] OR Goyal P[Author] OR Green JK[Author] OR Green JR[Author] OR Green SF[Author] OR Greene MH[Author] OR Greer JP[Author] OR Gregory SA[Author] OR Grimm BJ[Author] OR Grove MA[Author] OR Groves ML[Author] OR Gumina RJ[Author] OR Guo X[Author] OR Gupta DK[Author] OR Haake S[Author] OR Haas DW[Author] OR Haase VH[Author] OR Habermann RC[Author] OR Hackett A[Author] OR Haddad EV[Author] OR Hagaman DD[Author] OR Haglund NA[Author] OR Hall RL[Author] OR Halverson LP[Author] OR Hanker AB[Author] OR Hanlon A[Author] OR Hansen DE[Author] OR Hanson KL[Author] OR Hardman NC[Author] OR Harmon DB[Author] OR Harrelson PR[Author] OR Harrington DR[Author] OR Harris BD[Author] OR Harris RC[Author] OR Harrison DG[Author] OR Harrison FE[Author] OR Hartert TV[Author] OR Hathaway JW[Author] OR Hatzopoulos AK[Author] OR Hawiger J[Author] OR Hawkins DK[Author] OR Heibig J[Author] OR Heimburger DC[Author] OR Heitman E[Author] OR Helderman JH[Author] OR Heller LT[Author] OR Hellervik SM[Author] OR Hemnes AR[Author] OR Hendrickson CD[Author] OR Hensley RL[Author] OR Herrmann PH[Author] OR Higginbotham JN[Author] OR Hill MF[Author] OR Hines TE[Author] OR Hinton TJ[Author] OR Hock RL[Author] OR Holliday L[Author] OR Hong CC[Author] OR Hood RR[Author] OR Horn L[Author] OR Horowitz P[Author] OR Horst S[Author] OR Horton A[Author] OR Howard GA[Author] OR Hudson BB[Author] OR Huggins E[Author] OR Hughes SG[Author] OR Hulgan TM[Author] OR Hull PC[Author] OR Hung AM[Author] OR Hung RR[Author] OR Huston JW[Author] OR Ikizler TA[Author] OR Irani WN[Author] OR Ismail NM[Author] OR Israel DA[Author] OR Jackson JC[Author] OR Jagasia M[Author] OR Jagasia S[Author] OR Jansen VM[Author] OR Jennings HS[Author] OR Johnson CN[Author] OR Johnson DB[Author] OR Jones JL[Author] OR Kabagambe EK[Author] OR Kaiser AB[Author] OR Kalams SA[Author] OR Kalnas J[Author] OR Kanagasundram AN[Author] OR Kaplan HR[Author] OR Karlekar MB[Author] OR Karnett B[Author] OR Karpinos AJ[Author] OR Kassim AA[Author] OR Kawai VK[Author] OR Kearney-Gray KR[Author] OR Keebler ME[Author] OR Keedy VL[Author] OR Kelley MB[Author] OR Kendall PL[Author] OR Keswani AN[Author] OR Khalaf WF[Author] OR Kim JY[Author] OR King LE[Author] OR King LG[Author] OR Kinzig B[Author] OR Kipp AM[Author] OR Kirabo A[Author] OR Kirabo A[Author] OR Knapik EW[Author] OR Knollmann BC[Author] OR Kobayashi H[Author] OR Koethe JR[Author] OR Kolek MJ[Author] OR Kolli MK[Author] OR Kondo J[Author] OR Koonce JH[Author] OR Kripalani SB[Author] OR Kripalani SP[Author] OR Kronenberg MW[Author] OR Kroop SF[Author] OR Kropski J[Author] OR Kryshtal D[Author] OR Kurtz EG[Author] OR Laffer CL[Author] OR Lal H[Author] OR Lancaster LH[Author] OR Landsperger JS[Author] OR Lane J[Author] OR Lane RG[Author] OR Lang Kuhs K[Author] OR Langone AJ[Author] OR Larkin EK[Author] OR LaRue RW[Author] OR Lawson MA[Author] OR Lawson WE[Author] OR Legner VJ[Author] OR Lehman J[Author] OR Lenihan DJ[Author] OR Leonard M[Author] OR Lewis CM[Author] OR Lewis J[Author] OR Lewis SK[Author] OR Light RW[Author] OR Lind CD[Author] OR Lindenfeld J[Author] OR Linn CR[Author] OR Linton MF[Author] OR Lipps J[Author] OR Lipworth LP[Author] OR Liu YX[Author] OR Locklear CM[Author] OR Loh JT[Author] OR Long J[Author] OR Long M[Author] OR Lovly CM[Author] OR Loyd JE[Author] OR Lucas E[Author] OR Luo W[Author] OR Luther JM[Author] OR MacDonald JR[Author] OR MacLean C[Author] OR Madhur M[Author] OR Majka SM[Author] OR Major AS[Author] OR Maldonado F[Author] OR Mallal SA[Author] OR Maltz BE[Author] OR Manda RR[Author] OR Maquiling K[Author] OR Martin SF[Author] OR Martinez W[Author] OR Mason WR[Author] OR Massion PP[Author] OR Mathew S[Author] OR May JM[Author] OR May ME[Author] OR Mayberry LS[Author] OR Mayer IA[Author] OR Maynard WH[Author] OR McAbee SA[Author] OR McBean MR[Author] OR McClain MS[Author] OR Mccord JL[Author] OR McCroskey DJ[Author] OR McDaniel J[Author] OR McDonald MA[Author] OR McGowan CC[Author] OR McPherson JA[Author] OR McReynolds KM[Author] OR Meador BP[Author] OR Mendes LA[Author] OR Micheel CM[Author] OR Miller AN[Author] OR Miller JL[Author] OR Miller MS[Author] OR Miller RF[Author] OR Mills JB[Author] OR Milne GL[Author] OR Misra R[Author] OR Misra SK[Author] OR Mixon AS[Author] OR Mixon A[Author] OR Mohan S[Author] OR Monahan KJ[Author] OR Monahan S[Author] OR Montgomery JA[Author] OR Moolman KC[Author] OR Morgan DR[Author] OR Morgan DS[Author] OR Morgans AK[Author] OR Morrison MA[Author] OR Moslehi JJ[Author] OR Mosley JA[Author] OR Mosley JD[Author] OR Moutsios SA[Author] OR Muldowney JA[Author] OR Munoz D[Author] OR Murad AM[Author] OR Murff HJ[Author] OR Murphy BA[Author] OR Murray KT[Author] OR Muthian G[Author] OR Myers KJ[Author] OR Nadeau JH[Author] OR Naftilan AJ[Author] OR Nam YJ[Author] OR Nash R[Author] OR Nazarewicz RR[Author] OR Nelson GE[Author] OR Nelson JR[Author] OR Ness RM[Author] OR Neufeld L[Author] OR Neuss MN[Author] OR Newcomb DC[Author] OR Newman JH[Author] OR Nickels A[Author] OR Niswender KD[Author] OR Nohl AJ[Author] OR Noto JM[Author] OR Noto MJ[Author] OR Novitskiy SV[Author] OR Oates JA[Author] OR Obstein KL[Author] OR Odom HE[Author] OR Okafor HE[Author] OR Okamoto LE[Author] OR Olson A[Author] OR Oluwole O[Author] OR Ooi HH[Author] OR Ormseth MJ[Author] OR Osborn CY[Author] OR Pace D[Author] OR Pae D[Author] OR Paik PE[Author] OR Pandey AK[Author] OR Parker SR[Author] OR Parr S[Author] OR Patton H[Author] OR Payne DM[Author] OR Peach JP[Author] OR Peachey MR[Author] OR Pedchenko TV[Author] OR Pedchenko VK[Author] OR Peebles RS[Author] OR Peek RM[Author] OR Peggs KJ[Author] OR Pendergrast JL[Author] OR Pereira JK[Author] OR Perri RE[Author] OR Perry BA[Author] OR Person AK[Author] OR Peterson NB[Author] OR Pettit AC[Author] OR Phares JM[Author] OR Phillips EJ[Author] OR Piana RN[Author] OR Piazuelo MB[Author] OR Pierce HR[Author] OR Piercey A[Author] OR Pilkinton M[Author] OR Pinkston J[Author] OR Poe LT[Author] OR Pokidysheva E[Author] OR Pollice-Meservy JM[Author] OR Polosukhin VV[Author] OR Poole JS[Author] OR Porayko MK[Author] OR Potter MR[Author] OR Powers AC[Author] OR Powers JS[Author] OR Pozzi AA[Author] OR Prager JM[Author] OR Price JE[Author] OR Prudoff AJ[Author] OR Pugh ME[Author] OR Pulley JM[Author] OR Qian HZ[Author] OR Qian J[Author] OR Qiao H[Author] OR Quesada NC[Author] OR Raffanti SP[Author] OR Rahman J[Author] OR Ramanna N[Author] OR Ramsey H[Author] OR Rao SK[Author] OR Rathmell K[Author] OR Rebeiro PF[Author] OR Reddy NM[Author] OR Reddy SK[Author] OR Rexer BN[Author] OR Rice EA[Author] OR Rice TW[Author] OR Richardson TR[Author] OR Richmond BW[Author] OR Rickman OB[Author] OR Ridinger HA[Author] OR Robbins IM[Author] OR Robbins MA[Author] OR Robbins SG[Author] OR Robertson DH[Author] OR Roden DM[Author] OR Rolando LA[Author] OR Root CK[Author] OR Rosen SS[Author] OR Ross TL[Author] OR Rothman RL[Author] OR Roumie CL[Author] OR Rowan BH[Author] OR Rubin DH[Author] OR Russell SB[Author] OR Rybczyk GK[Author] OR Saavedra PJ[Author] OR Sacks SB[Author] OR Salloum JG[Author] OR Salmony B[Author] OR Sanghani N[Author] OR Sastre EA[Author] OR Satyanarayana G[Author] OR Savani BN[Author] OR Savona MR[Author] OR Scalise ML[Author] OR Scanga AE[Author] OR Schaefer HM[Author] OR Schlendorf KH[Author] OR Schneider BG[Author] OR Schneider NJ[Author] OR Schneider SE[Author] OR Schnelle JF[Author] OR Scholl LA[Author] OR Schreier RL[Author] OR Schulman G[Author] OR Schwartz DA[Author] OR Scott JD[Author] OR See R[Author] OR Seger DL[Author] OR Seidner DL[Author] OR Seitz MF[Author] OR Semler M[Author] OR Sengsayadeth S[Author] OR Serafin WE[Author] OR Sergent JS[Author] OR Serie SS[Author] OR Sevin C[Author] OR Shackelford CE[Author] OR Shackleford L[Author] OR Shapman AM[Author] OR Shaver C[Author] OR Sheller JR[Author] OR Shen ST[Author] OR Shepherd ME[Author] OR Shibao CA[Author] OR Shoemaker B[Author] OR Shrubsole MJ[Author] OR Shu XO[Author] OR Sibler KL[Author] OR Siew ED[Author] OR Sika M[Author] OR Silva-Hale A[Author] OR Silver HJ[Author] OR Simmons SF[Author] OR Simpson T[Author] OR Singh B[Author] OR Singh J[Author] OR Singh K[Author] OR Singleton A[Author] OR Slosky DA[Author] OR Smalley WE[Author] OR Smith AL[Author] OR Smith JR[Author] OR Smith MK[Author] OR Smith SA[Author] OR Smith SJ[Author] OR Smith TA[Author] OR Snook BM[Author] OR Song W[Author] OR Sopko KL[Author] OR Sorey MR[Author] OR Southard-Smith EM[Author] OR Sparkman CC[Author] OR Spicer JV[Author] OR Spickard, III WA[Author] OR Spires SS[Author] OR Sponsler KE[Author] OR Spradlin NM[Author] OR Stafford JM[Author] OR Stebbins WG[Author] OR Steigelfest E[Author] OR Stein CM[Author] OR Sterling JA[Author] OR Sterling TR[Author] OR Stewart RC[Author] OR Stiles RA[Author] OR Stober CV[Author] OR Stone WJ[Author] OR Strickland SA[Author] OR Su TY[Author] OR Su YR[Author] OR Sumner EL[Author] OR Sussman CR[Author] OR Swift MD[Author] OR Swiggart WH[Author] OR Takahashi T[Author] OR Talati MH[Author] OR Talbot HK[Author] OR Talbot TR[Author] OR Tang Q[Author] OR Tanjore H[Author] OR Tanner SB[Author] OR Tao H[Author] OR Tarvin EM[Author] OR Theobald CM[Author] OR Thomas JW[Author] OR Thomas LD[Author] OR Thompson TA[Author] OR Timken KJ[Author] OR Tindle H[Author] OR Titus WP[Author] OR Titze J[Author] OR Toki S[Author] OR Tolle JJ[Author] OR Umeukeje E[Author] OR Utz AL[Author] OR Vaezi MF[Author] OR van der Heijden Y[Author] OR Vanacore RM[Author] OR Vasilevskis EE[Author] OR Veach RA[Author] OR Velasquez AM[Author] OR Vickers KC[Author] OR Vinson JM[Author] OR Voziyan PA[Author] OR Wagnon JH[Author] OR Walker AM[Author] OR Wallace DE[Author] OR Walsh DW[Author] OR Walston CE[Author] OR Wang TJ[Author] OR Wang Y[Author] OR Wang Z[Author] OR Ware LB[Author] OR Warner JL[Author] OR Wasden CM[Author] OR Watson PL[Author] OR Weaver EO[Author] OR Wellons M[Author] OR Wells Q[Author] OR Wen W[Author] OR West DC[Author] OR West JD[Author] OR West JJ[Author] OR Wester CW[Author] OR White BJ[Author] OR White KE[Author] OR Whitfield TC[Author] OR Whitman JH[Author] OR Wiese DM Wiesner GL[Author] OR Wigger MA[Author] OR Wilkerson K[Author] OR Wilkins CH[Author] OR Wilkins KL[Author] OR Williams CS[Author] OR Williams ME[Author] OR Wilson KT[Author] OR Wilson M[Author] OR Wilson MA[Author] OR Wilson MH[Author] OR Wirth DC[Author] OR Womack BD[Author] OR Woodard LE[Author] OR Woods M[Author] OR Wooldridge AR[Author] OR Wooldridge KT[Author] OR Wright HG[Author] OR Wright PW[Author] OR Wright S[Author] OR Wroblewski LE[Author] OR Wu P[Author] OR Wyman KW[Author] OR Xu XC[Author] OR Yachimski PS[Author] OR Yancey PG[Author] OR Yang G[Author] OR Yang T[Author] OR Yang Y[Author] OR Yao B[Author] OR Yarbrough MI[Author] OR Yazlovitskaya EM[Author] OR York SJ[Author] OR Young RT[Author] OR Yu D[Author] OR Zaidi SS[Author] OR Zaka OO[Author] OR Zalawadiya SK[Author] OR Zeng F[Author] OR Zent R[Author] OR Zhang MZ[Author] OR Zhang Q[Author] OR Zheng W[Author] OR Zhong X[Author] OR Zhou W[Author] OR Zic JA[Author] OR Zienkiewicz J[Author] OR Zinkel SS[Author] OR Zoffuto TM[Author] OR Zwerner JP[Author])) AND (("Nature methods"[Jour] OR "N Engl J Med"[jour] OR "Nature"[Jour] OR "Nature genetics"[Jour] OR "Cell"[Jour] OR "Lancet"[Jour] OR "Science"[Jour] OR "Nature biotechnology"[Jour] OR "JAMA"[Jour] OR "Nature medicine"[Jour] OR "Nature nanotechnology"[Jour] OR "Nature immunology"[Jour] OR "Cancer cell"[Jour] OR "Cell stem cell"[Jour] OR "Immunity"[Jour] OR "Nature cell biology"[Jour] OR "J Clin Oncol" OR "Cell metabolism"[Jour] OR "Nature methods"[Jour] OR "Nature chemical biology"[Jour] OR "Lancet Infect Dis"[jour] OR "J Clin Invest"[jour] OR "Circulation"[jour] OR "ann intern med" OR "arch intern med" OR "blood"[Jour] OR "brit med j" OR "circ res"[jour] OR "gastroenterology"[Jour] OR "j allergy clin immunol" OR "j am coll cardiol" OR "j am soc nephrol" OR "plos med" OR "Proc Natl Acad Sci U S A"[Jour]))) AND "vanderbilt university"[Affiliation]
Subscribe to Recent Discoveries feed