tbuckley/cabot-search huggingface dataset:
Abstract 18696: Regional Distribution of Cerebral White Matter Hyperintensities in HFrEF and HFpEF
Authors: Kelsey Melah, Chooza Moon, Sterling C Johnson, Lisa C Bratzke
Journal: Circulation (2015)

Introduction: Patients with heart failure (HF) commonly suffer from cognitive impairment. White matter hyperintensities (WMHs) are associated with cognitive decline, cardiovascular risk in healthy aging and CNS disorders. Studies have shown that patients with heart failure with reduced ejection fraction (HFrEF) have greater volume of WMHs compared to controls. However, little is known about the distribution and size of WMHs in patients with heart failure with preserved ejection fraction (HFpEF). This study utilizes quantitative neuroimaging analysis to examine volume and regional distribution of WMHs between patients with HFrEF, HFpEF, and controls. Methods: Thirty-nine HF patients (mean age=68.2) and 28 controls (mean age=67.4) underwent high-resolution T-2 weighted fluid attenuated inversion recovery imaging. Volume of WMHs was calculated using the Lesion Segmentation Tool in Statistical Parametric Mapping 8 (SPM8). Total volume of WMHs was divided by intracranial volume to calculate WMH ratio (WMHr). Regional analysis of WMHs was performed using a multiple regression analysis of lesion probability maps in SPM8. Imaging results were family wise error corrected for multiple comparisons. Results: One-way ANCOVA revealed that individuals with HF had greater WMHr compared to controls, controlling for age, sex, and comorbid burden (p=0.001). Further analysis revealed that there was no significant difference in WMHr between HFrEF and HFpEF, although both groups had significantly greater WMHr compared to controls (p=0.005). Individuals with HF were more likely to have WMHs in the right cingulum (p&lt;0.001) and right genu (p=0.001) of the corpus callosum. There were no differences in distribution of WMHs between patients with HRrEF or HFpEF. Conclusion: Patients with HFrEF or HFpEF have greater WMHr compared to controls and WMHs are likely to be located in the right cingulum and genu. The cingulum and genu are white matter tracts that are essential for memory and cognitive control. In patients with HF, the damage to these areas caused by WMHs may be associated changes in cognition. Future studies are needed to further examine the relationship between cognition and WMHs in HF patients and the mechanistic relationship between HF and WMHs.
Abstract 137: Ghrhr is a Cell-surface Marker of Human Pluripotent Stem Cell-derived Cardiomyogenic Precursors
Authors: Konstantinos E Hatzistergos, Anastasia Vedenko, Krystalenia Valasaki, Wayne Balkan, Joshua M Hare
Journal: Circulation Research (2017)

Introduction: A major roadblock for generating human pluripotent stem cell (hPSCs) derivatives highly enriched in cardiomyogenic precursors (CPCs), has been the lack of CPC-specific cell surface markers. Hypothesis: Based on observations that adult CPCs are responsive to growth hormone-releasing hormone (GHRH) signaling, we hypothesized that the GHRH receptor (GHRHR) is a specific cell-surface marker for hPSC-derived CPCs. Methods: We performed temporal analysis of GHRHR expression in an in-vitro model of human cardiogenesis using induced hPSCs (hiPSCs) and SOX10::GFP embryonic hPSCs (hESCs) ; and mouse ( in-vivo ) cardiogenesis in wild-type (WT), MEF2c-AHF-Cre, Wnt1-Cre2 and cKit-CreERT2/+ reporter mice. Results: Gene expression and confocal immunofluorescence analyses during chemically-defined, stage-specific, cardiac lineage differentiation indicated that GHRHR is not expressed in undifferentiated hiPSCs or during specification into primitive streak-like Brachyury + or Mesp1 + precardiac cells; but is induced in cardiogenic mesoderm-like cells, at the stage of commitment into NKX2.5 + and/or ISL1 + CPCs ( p =0.001) and persists in Troponin-T + cardiomyocytes. Similarly, experiments modeling cardiac neural crest (CNC) with SOX10::GFP hESCs indicated that GHRHR is not expressed by GFP + CNCs but is induced following differentiation into NKX2.5 + and/or ISL1 + derivatives. Importantly, stimulation with 1μm recombinant GHRH during days 5-7 of hiPSCs differentiation increased NKX2.5 expression 2.5-fold, an effect that was abolished by exposure to 1μM Somatostatin, a GHRH antagonist ( p =0.0009). Last, in vivo analyses in WT , MEF2c-AHF-Cre, Wnt1-Cre2 and cKit-CreERT2/+ reporter embryonic and postnatal hearts corroborated that GHRHR specifically marks NKX2.5 + mesoderm- and CNC-lineage descendants in vivo, whereas GHRHR is not expressed by Wnt1-Cre2 and cKit-CreERT2/+ CNCs descendants that are Nkx2.5 – . Conclusions: Together these findings indicate that GHRHR is universally expressed by NKX2.5 + /ISL1 + CPCs and cardiomyocytes of both mesoderm and CNC origin. Therefore, GHRHR appears to be a valuable cell-surface marker for the selection and enrichment of CPCs from hPSCs for biomedical and regenerative medicine applications.
Abstract 17101: Genetic Testing as an Effective Diagnostic Tool for Familial Hypercholesterolemia
Authors: Tami Johnston, Andy Castro, Lily Hoang, Brittany Dougall, Jessica Gage, Jill Dolinsky, Christian Antolik
Journal: Circulation (2017)

Introduction: Hypercholesterolemia is characterized by high levels of plasma low density lipoprotein (LDL) in the blood and an increased risk for coronary artery disease (CAD). Familial hypercholes...
The Shwachman-Diamond Syndrome Registry: Hematologic Complications
Authors: Kasiani C. Myers, Elissa Muse Furutani, Sara Loveless, Maggie Malsch, Ashley Galvin, Ellie Fratt, Jordan Larson, Jacob Cotton, Leah Cheng, Kelly McIntosh, Joan Moore, Leann Mount, Rabi Hanna, Winfred Wang, Alison A. Bertuch, Stella M. Davies, Akiko Shimamura
Journal: Blood (2018)
Review: Adjuvant recombinant subunit vaccine prevents herpes zoster more than live attenuated vaccine in adults ≥ 50 years
Authors: Henry S. Sacks
Journal: Annals of Internal Medicine (2019)

Source Citation Tricco AC, Zarin W, Cardoso R, et al. Efficacy, effectiveness, and safety of herpes zoster vaccines in adults aged 50 and older: systematic review and network meta-analysis. BMJ. 2018;363:k4029. 30361202
Epithelial Markers can Reflect Esophageal Fibrosis Score in Pediatric Eosinophilic Esophagitis
Authors: Lucas Dohil, Renée M. Rawson, Prerana Williamson, Robert Newbury, Richard Kurten, Ranjan Dohil, Seema S. Aceves
Journal: Journal of Allergy and Clinical Immunology (2019)
Review: Thyroid hormone therapy does not improve QoL or symptoms in subclinical hypothyroidism
Authors: Bruce E. Johnson
Journal: Annals of Internal Medicine (2019)

Source Citation Feller M, Snel M, Moutzouri E, et al. Association of thyroid hormone therapy with quality of life and thyroid-related symptoms in patients with subclinical hypothyroidism: a systematic review and meta-analysis. JAMA. 2018;320:1349-59. 30285179
Tumor pH and Protein Concentration Contribute to the Signal of Amide Proton Transfer Magnetic Resonance Imaging
Authors: Kevin J. Ray, Manon A. Simard, James R. Larkin, James Coates, Paul Kinchesh, Sean C. Smart, Geoff S. Higgins, Michael A. Chappell, Nicola R. Sibson
Journal: Cancer Research (2019)

Abnormal pH is a common feature of malignant tumors and has been associated clinically with suboptimal outcomes. Amide proton transfer magnetic resonance imaging (APT MRI) holds promise as a means to noninvasively measure tumor pH, yet multiple factors collectively make quantification of tumor pH from APT MRI data challenging. The purpose of this study was to improve our understanding of the biophysical sources of altered APT MRI signals in tumors. Combining
Human Fetal TNF-α-Cytokine-Producing CD4+ Effector Memory T Cells Promote Intestinal Development and Mediate Inflammation Early in Life
Authors: Renée R.C.E. Schreurs, Martin E. Baumdick, Adrian F. Sagebiel, Max Kaufmann, Michal Mokry, Paul L. Klarenbeek, Nicola Schaltenberg, Fenja L. Steinert, Jorik M. van Rijn, Agata Drewniak, Sarah-May M.L. The, Roel Bakx, Joep P.M. Derikx, Niek de Vries, Willemijn E. Corpeleijn, Steven T. Pals, Nicola Gagliani, Manuel A. Friese, Sabine Middendorp, Edward E.S. Nieuwenhuis, Konrad Reinshagen, Teunis B.H. Geijtenbeek, Johannes B. van Goudoever, Madeleine J. Bunders
Journal: Immunity (2019)
Reply:
Authors: Eun‐Jeong Joo, Yoosoo Chang, Seungho Ryu
Journal: Hepatology (2017)

Potential conflict of interest: Nothing to report. We thank Drs. Wang and Kao for their interest in our work and valuable input. In our cohort study, we found a lower risk for incident nonalcoholic fatty liver disease (NAFLD) in hepatitis B virus (HBV) surface antigen (HBsAg)–positive patients, even if they presented with higher body mass index and higher obesity.1 Regarding insulin resistance, a key factor in NAFLD pathogenesis, baseline insulin resistance using homeostatic model assessment‐insulin resistance (HOMA‐IR) was not different between HBsAg‐positive and HBsAg‐negative patients.1 In the mixed model for evaluating the longitudinal effects of HBV infection on changes in HOMA‐IR from baseline and until either the development of NAFLD or the last visit, increases in HOMA‐IR levels over time did not differ between HBsAg‐positive and HBsAg‐negative subjects.1 On the other hand, favorable lipid profiles both at baseline and during follow‐up in HBsAg‐positive subjects were observed1 and were consistent with previous reports.2 These findings support the idea that altered lipid metabolism in HBV infection may contribute to lowering the incidence of NAFLD. However, further studies are required to determine HBV's role in the pathogenesis of NAFLD considering lipid metabolism and undetermined mechanisms. Even though we found a lower risk of NAFLD in HBsAg‐positive subjects, it is still important to identify modifiable risk factors for NAFLD in HBV‐infected individuals.4 We used a parametric Cox model to identify the risk factors for NAFLD separately in both HBsAg‐positive and HBsAg‐negative subjects. The HOMA‐IR level increased the development of NAFLD in HBsAg‐negative subjects but not in HBV‐infected individuals. Elevated body mass index level and unfavorable lipid profiles with high levels of total cholesterol and triglycerides and low levels of high‐density lipoprotein cholesterol were significantly associated with an increased incidence of NAFLD in both HBsAg‐positive and HBsAg‐negative subjects, suggesting that prevention of obesity and dyslipidemia is still important for reducing NAFLD regardless of HBV infection status (Table 1). Table 1 - Risk Factors for Incident NAFLD Stratified by HBsAg Positivity Among HBsAg‐Negative Subjects Among HBsAg‐Positive Subjects Variables Hazard Ratio (95% CI) Hazard Ratio (95% CI) Body mass index (kg/m2) 1.19 (1.18‐1.20) 1.18 (1.15‐1.21) Total cholesterol (mg/dL) 1.003 (1.003‐1.004) 1.005 (1.004‐1.008) HDL‐C (mg/dL) 0.99 (0.98‐0.99) 0.98 (0.97‐0.99) Triglycerides (mg/dL) 1.002 (1.001‐1.002) 1.002 (1.001‐1.003) HOMA‐IR 1.22 (1.20‐1.24) 1.03 (0.97‐1.09) Glucose (mg/dL) 1.00 (0.99‐1.00) 1.00 (0.99‐1.01) Systolic blood pressure (mm Hg) 0.99 (0.99‐1.001) 1.00 (0.99‐1.01) Estimated from parametric Cox models. The multivariate model was adjusted for age, sex, smoking status, alcohol intake, regular exercise, education level, and all other variables listed for the model.Abbreviations: CI, confidence interval; HDL‐C, high‐density lipoprotein cholesterol.
Eosinophilic Esophagitis: A Potentially Severe Chronic Disease With Rapid Evolution Also In Children
Authors: Ana Laura Mendes Becker Andrade, Marina Mayumi Vendrame Takao, Carla de Oliveira Parra Duarte, Thais Longo de Morais Teixeira, Maria Marluce dos Santos Vilela, Marcos Tadeu Nolasco da Silva, Elizete Aparecida Lomazi, Maria Angela Bellomo Brandão, Adriana Gut Lopes Riccetto
Journal: Journal of Allergy and Clinical Immunology (2019)
Inhibiting Glutamine-Dependent mTORC1 Activation Ameliorates Liver Cancers Driven by β-Catenin Mutations
Authors: Adeola O. Adebayo Michael, Sungjin Ko, Junyan Tao, Akshata Moghe, Hong Yang, Meng Xu, Jacquelyn O. Russell, Tirthadipa Pradhan-Sundd, Silvia Liu, Sucha Singh, Minakshi Poddar, Jayvir S. Monga, Pin Liu, Michael Oertel, Sarangarajan Ranganathan, Aatur Singhi, Sandra Rebouissou, Jessica Zucman-Rossi, Silvia Ribback, Diego Calvisi, Natalia Qvartskhava, Boris Görg, Dieter Häussinger, Xin Chen, Satdarshan P. Monga
Journal: Cell Metabolism (2019)
Neoantigen screening identifies broad TP53 mutant immunogenicity in patients with epithelial cancers
Authors: Parisa Malekzadeh, Anna Pasetto, Paul F. Robbins, Maria R. Parkhurst, Biman C. Paria, Li Jia, Jared J. Gartner, Victoria Hill, Zhiya Yu, Nicholas P. Restifo, Abraham Sachs, Eric Tran, Winifred Lo, Robert P.T. Somerville, Steven A. Rosenberg, Drew C. Deniger
Journal: Journal of Clinical Investigation (2019)

The adoptive cell transfer of select tumor-infiltrating lymphocytes (TILs) for personalized immunotherapy can mediate long-term objective tumor regressions in patients with metastatic melanoma, bile duct, cervix, colon, and breast cancers (1–5). These clinical responses are likely mediated by recognition of mutated gene products termed neoantigens because they are absent in normal tissues. Intratumoral T cell responses to mutated neoantigens identified thus far have been unique to the patient, i.e., they are private mutations not identified in other patients’ tumors, except for a neoepitope arising from the KRASG12D driver mutation (1, 3). However, it is largely unknown whether naturally occurring T cells within tumors recognize other shared mutated neoantigens expressed by cancers of unrelated patients.

Across all cancer types, TP53 is the most commonly mutated gene, but mutations occur throughout the gene with preference in the DNA binding domain (6, 7). Therapeutic approaches evaluating small-molecule inhibitors and T cells targeting both WT and mutant p53 tumors in mouse models have been described (8–11). Preliminary studies provided some evidence that mutated TP53 could be recognized by peripheral blood T cells after in vitro stimulation and in vivo vaccination (12–14). However, evidence of immune responses to mutated TP53 within human tumors is limited even though most tumors will express a TP53 mutation. We previously reported patient-specific neoantigen screening in 7 patients with metastatic ovarian cancer, 2 of whom had mutated TP53 neoantigens restricted by HLA-DRB3*02:02 (15, 16). Here, we developed a novel strategy to systematically and comprehensively analyze intratumoral T cell responses to defined TP53 hot spot mutations independent of other tumor mutations in 133 new patients with multiple tumor types. The goal was to translate these cells or their TCR genes into broadly applicable adoptive cellular therapies for common epithelial malignancies.
Association of Survival With Femoropopliteal Artery Revascularization With Drug-Coated Devices
Authors: Eric A. Secemsky, Harun Kundi, Ido Weinberg, Michael R. Jaff, Anna Krawisz, Sahil A. Parikh, Joshua A. Beckman, Jihad Mustapha, Kenneth Rosenfield, Robert W. Yeh
Journal: JAMA Cardiology (2019)

In a recent meta-analysis of randomized clinical trials, femoropopliteal artery revascularization with paclitaxel drug-coated devices was associated with increased long-term all-cause mortality compared with non-drug-coated devices. However, to our knowledge, these findings have not been replicated in other data sources and may be subject to confounding from missing data associated with patient withdrawal and loss to follow-up.To evaluate differences in all-cause mortality between patients who were treated with drug-coated devices vs non-drug-coated devices for femoropopliteal artery revascularization.This nationwide, multicenter retrospective cohort study included 16 560 Centers for Medicare and Medicaid Services beneficiaries who were admitted for femoropopliteal artery revascularization from January 1, 2016, to December 31, 2016. All-cause mortality was analyzed through September 30, 2017.Drug-coated devices (drug-eluting stent [DES] or drug-coated balloon [DCB]) compared with non-drug-coated devices (bare metal stent or uncoated percutaneous transluminal angioplasty balloon).The primary outcome was all-cause mortality analyzed through the end of follow-up.Among 16 560 patients treated at 1883 hospitals, the mean (SD) age was 72.9 (11) years, 7734 (46.7%) were men, 12 232 (73.9%) were white, 8222 (49.7%) currently or had previously used tobacco, 9817 (59.3%) had diabetes, and 8450 (51.0%) had critical limb ischemia (CLI). Drug-coated devices were used in 5989 participants (36.2%). The median follow-up was 389 days (interquartile range, 277-508 days). Among all patients, treatment with drug-coated devices was associated with a lower cumulative incidence of all-cause mortality compared with treatment with non-drug-coated devices through 600 days postprocedure (32.5% vs 34.3%, respectively; log-rank P = .007). Similar survival trends were observed when treatment was stratified by using a DCB alone or DES with or without DCB. After multivariable adjustment, drug-coated devices were not associated with a difference in all-cause mortality compared with non-drug-coated devices (hazard ratio [HR], 0.97; 95% CI, 0.91-1.04; P = .43). These findings were consistent among those with CLI (HR, 0.93; 95% CI, 0.85-1.01; P = .09) or without CLI (HR, 0.94; 95% CI, 0.85-1.03; P = .20), and for those treated with DCB alone (HR, 0.94; 95% CI, 0.86-1.03; P = .17) or DES with or without DCB (HR, 0.97; 95% CI, 0.89-1.06; P = .48).In this large nationwide analysis of Centers for Medicare and Medicaid Services beneficiaries, there was no evidence of increased all-cause mortality following femoropopliteal artery revascularization with drug-coated devices compared with non-drug-coated devices.
Diffuse Large B-Cell Lymphoma, Not Otherwise Specified: Discordance between Histology and Flow Cytometry in Bone Marrow Examination at Diagnosis
Authors: Fernando Martín Moro, Miguel Piris-Villaespesa, Monica Garcia Cosio, Jesus Villarrubia, Juan Marquet Palomanes, Ana Lario Arribas, Eulalia Rodríguez Martín, María Calbacho, Irene Garcia-Garcia, Berta Mercedes Michael Fernández, Carla Martínez-Geijo Román, Kyra Velázquez-Kennedy, Alejandro Sanz, Pilar Herrera Puente, Gemma Moreno Jiménez, Jose Valentín García Gutiérrez, Javier Lopez Jimenez
Journal: Blood (2018)
Safety of compression therapy using newly developed gloves for oxaliplatin induced neuropathy prevention.
Authors: Yukinori Koyama, Michina Morioka, Yuri Tobaru, Yusuke Sakura, Mikiko Fukumoto, Ayana Nagamine, Kuniaki Hattori, Itsuki Taira, Norimitsu Shimada, Koshi Kawakami, Shigeru Tsuyuki, Akiyoshi Kanazawa
Journal: Journal of Clinical Oncology (2019)

501 Background: Oxaliplatin (l-OHP) is a key drug commonly used in primary and metastatic colorectal cancer treatment. However, l-OHP is associated with non-hematological adverse effects, including peripheral neuropathy (PN). About 90% of patients who received l-OHP experience PN after single dose of l-OHP and PN is likely to be negatively associated with quality of life. There is no established effective prophylactic management for chemotherapy induced PN according to the 2014 American Society of Clinical Oncology (ASCO) guideline. Recently, compression of hands during injection of drugs has been reported to be effective for chemotherapy induced PN. We developed new gloves for compression therapy which are reusable and low cost. We prospectively analyzed the safety of the gloves. Methods: Patients who received l-OHP were eligible for this phase Ⅰ study. Wrist and hand size were measured and appropriate size of gloves were selected. The pressure of hands is estimated as 20-33 hPa. Patients start to wear the gloves on both hands, from 30 min before the injection of l-OHP until 30 min after the injection. Peripheral neuropathy was evaluated at each treatment cycle using common terminology criteria for adverse events (CTCAE) version 4.0. Results: Between October 2017 and August 2018, fourteen patients (median age 66 years [range 39– 79years], 7 male and 7 female) were enrolled and were evaluated. No patients withdrew from this study. No safety concerns were identified for any safety variables assessed during the trial. CTCAE grade 2 or higher sensory PN was observed in four (28.6%) patients. The average time until grade 1 or more neuropathy appeared was 27.8 days and average dose of l-OHP was 225mg. Conclusions: Compression therapy by the new gloves had no safety concerns, demonstrating a profile favorable for further development for prevention of oxaliplatin induced PN. Clinical trial information: 000029671.
Serum leptin levels reflect the severity of eosinophilic rhinosinusitis according to Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis Study (JESREC Study)
Authors: Yoshimasa Imoto, Tetsuji Takabayashi, Yukinori Kato, Masafumi Sakashita, Kanako Yoshida
Journal: Journal of Allergy and Clinical Immunology (2019)
Abstract 14967: PKA-Phosphorylation of Hsp20 is Associated With Detrimental Cardiac Remodeling and Early Death
Authors: George Gardner, Guan-Sheng Liu, Jiang Qian, Min Jiang, Wen-Feng Cai, Michael Tranter, Guo-Chang Fan, Jack Rubinstein, Evangelia Kranias
Journal: Circulation (2016)

Introduction: Heat shock protein 20 (Hsp20) enhances cardiac contractility through inhibition of protein phosphatase 1 (PP1) and elicits protection under stress conditions. Hsp20 is also the only s...
Abstract 17345: Impaired Coronary Flow Reserve on 82Rubidium Positron Emission Tomography Imaging Predicts Mortality in Heart Transplant Recipients
Authors: Attila Feher, Ajay Srivastava, Pravien Khanna, Edward Miller, Yi-Hwa Liu, Forrester Lee, Albert J Sinusas
Journal: Circulation (2017)

Introduction: Cardiac allograft vasculopathy (CAV) is the major determinant of late mortality in heart transplant (HT) patients. Given the global epicardial and microvascular involvement in CAV, my...
A Map of Human Type 1 Diabetes Progression by Imaging Mass Cytometry
Authors: Nicolas Damond, Stefanie Engler, Vito R.T. Zanotelli, Denis Schapiro, Clive H. Wasserfall, Irina Kusmartseva, Harry S. Nick, Fabrizio Thorel, Pedro L. Herrera, Mark A. Atkinson, Bernd Bodenmiller
Journal: Cell Metabolism (2019)