tbuckley/cabot-search huggingface dataset:
Alcoholic and non-alcoholic fatty liver disease and associations with coronary artery calcification: evidence from the Kangbuk Samsung Health Study
Authors: Yoosoo Chang, Seungho Ryu, Ki-Chul Sung, Yong Kyun Cho, Eunju Sung, Han-Na Kim, Hyun-Suk Jung, Kyung Eun Yun, Jiin Ahn, Hocheol Shin, Sarah Helen Wild, Christopher D Byrne
Journal: Gut (2018)

Recent evidence suggests that alcoholic fatty liver disease (AFLD) and non-alcoholic fatty liver disease (NAFLD) may differentially affect risk of cardiovascular mortality. To investigate whether early liver disease due to AFLD or NAFLD have similar or dissimilar effects on risk of early coronary artery atherosclerosis, we have investigated the associations between AFLD and NAFLD and coronary artery calcium (CAC).A cross-sectional study was performed in 105 328 Korean adults who attended a health check-up programme. CAC score was assessed using CT, daily alcohol intake was recorded as grams/day and liver fat by ultrasound. Logistic regression model was used to calculate ORs with 95% CIs for prevalent CAC.Both NAFLD and AFLD were positively associated with CAC score. After adjusting for potential confounders, multivariable-adjusted OR (95% CIs) for CAC >0 comparing NAFLD and AFLD to the reference (absence of both excessive alcohol use and fatty liver disease) were 1.10 (95% CI 1.05 to 1.16) and 1.20 (95% CI 1.11 to 1.30), respectively. In post hoc analysis, OR (95% CI) for detectable CAC comparing AFLD to NAFLD was 1.09 (95% CI 1.01 to 1.17). Associations of NAFLD and AFLD with CAC scores were similar in both non-obese and obese individuals without significant interaction by obesity (p for interaction=0.088). After adjusting for homeostasis model assessment of insulin resistance and high-sensitivity C reactive protein, the associations between fatty liver disease and CAC scores remained statistically significant.In this large sample of young and middle-aged individuals, early liver disease due to NAFLD and AFLD were both significantly associated with the presence of coronary artery calcification.
<scp>IL</scp>‐27 signaling deficiency develops Th17‐enhanced Th2‐dominant inflammation in murine allergic conjunctivitis model
Authors: Xin Chen, Ruzhi Deng, Wei Chi, Xia Hua, Fan Lu, Fang Bian, Ning Gao, Zhijie Li, Stephen C. Pflugfelder, Cintia S. de Paiva, De‐Quan Li
Journal: Allergy (2018)

Abstract Background While most studies focus on pro‐allergic cytokines, the protective role of immunosuppressive cytokines in allergic inflammation is not well elucidated. This study was to explore a novel anti‐inflammatory role and cellular/molecular mechanism of IL ‐27 in allergic inflammation. Methods A murine model of experimental allergic conjunctivitis ( EAC ) was induced in BALB /c, C57 BL /6 or IL ‐27Rα‐deficient ( WSX ‐1 −/− ) mice by short ragweed pollen, with untreated or PBS ‐treated mice as controls. The serum, eyeballs, conjunctiva, cervical lymph nodes ( CLN s) were used for study. Gene expression was determined by RT ‐ qPCR , and protein production and activation were evaluated by immunostaining, ELISA and Western blotting. Results Typical allergic manifestations and stimulated thymic stromal lymphopoietin ( TSLP ) signaling and Th2 responses were observed in ocular surface of EAC models in BALB /c and C57 BL /6 mice. The decrease of IL ‐27 at mRNA ( IL ‐27/ EBI 3) and protein levels were detected in serum, conjunctiva and CLN , as evaluated by RT ‐ qPCR , immunofluorescent staining, ELISA and Western blotting. EAC induced in WSX ‐1 −/− mice showed aggravated allergic signs with higher TSLP ‐driven Th2‐dominant inflammation, accompanied by stimulated Th17 responses, including IL ‐17A, IL ‐17F, and transcription factor ROR γt. In contrast, Th1 cytokine IFN γ and Treg marker IL ‐10, with their respective transcription factors T‐bet and foxp3, were largely suppressed. Interestingly, imbalanced activation between reduced phosphor (P)‐ STAT 1 and stimulated P‐ STAT 6 were revealed in EAC , especially WSX ‐1 −/− ‐ EAC mice. Conclusion These findings demonstrated a natural protective mechanism by IL ‐27, of which signaling deficiency develops a Th17‐type hyperresponse that further aggravates Th2‐dominant allergic inflammation.
Abstract 13273: Rising Violent Crime and Changes in Blood Pressure in Chicago
Authors: Elizabeth L Tung, Stephanie A Besser, Rhys Chua, Marynia Kolak, Stacy T Lindau, Emeka Anyanwu, James K Liao, Corey E Tabit
Journal: Circulation (2018)

Introduction: People living in areas with high rates of crime tend to have high rates of hypertension. This association can be explained, in part, by allostatic load theory, which describes how blo...
Real-World Outcomes for Transplant-Ineligible Patients with Newly Diagnosed Multiple Myeloma Treated with Lenalidomide, Bortezomib, and Dexamethasone, or Bortezomib and Dexamethasone: An Enhanced Electronic Health Records Database Analysis
Authors: Ajai Chari, Brian Ung, Marc Tian, Amit Agarwal, Kejal Parikh
Journal: Blood (2018)
Climate change is outpacing response, warn experts
Authors: Jacqui Wise
Journal: BMJ (2018)

The current slow progress in reducing global emissions of greenhouse gases threatens human lives and could disrupt and overwhelm health services, warns a major report from international experts.1

The warning comes as the Met Office predicts that the UK would experience wetter winters and summers that could be up to 5.4°C hotter by 2070 as a result of climate change.2 Its climate projections say that sea levels in London could rise by up to 1.15 m by 2100 under a high emission scenario.

The report of the Lancet Countdown on health and climate change, the result of a collaboration of 27 leading academic institutions, the UN, and intergovernmental agencies, …
New Treatment Options in Advanced Stage Follicular Lymphoma
Authors: Kai Hübel, Gilles Salles, Robert Marcus, Pier Luigi Zinzani, Martin Dreyling
Journal: HemaSphere (2018)

Follicular lymphoma is one of the most common non-Hodgkin's lymphomas with an expected survival of more than 20 years for the majority of patients. This impressive outcome has been achieved with the introduction of immunochemotherapy, as first line treatment with remissions lasting over 8 years, followed by other treatment options at first or subsequent relapse. However, certain groups of patients still have a poor prognosis. In recent years the efficacy of chemotherapy regimens has been augmented by new compounds selectively targeting the cell surface, intracellular pathways, and/or the microenvironment. Some of these are beginning to change the therapeutic landscape. This review summarizes prognostic factors in follicular lymphoma in order to identify patients with greatest medical need for these new treatment options and reviews recent data from prospective clinical studies testing new agents in first-line and relapsed follicular lymphoma. Finally, we assess the current role of immunochemotherapy and discuss the requirements for future clinical trials.
Abstract 16524: Cardiac MRI Evaluation of Myocardial Deformation in Repaired Tetralogy of Fallot Provides Insight Into Right Ventricular Mechanics
Authors: Benjamin Goot, Kumaradevan Punithakumar, Edythe Tham, Michelle Noga
Journal: Circulation (2015)

Introduction: Pulmonary regurgitation or stenosis after repaired tetralogy of Fallot (TOF) impacts the long-term ventricular mechanics. Our objective was to measure RV myocardial deformation using novel CMR software in repaired TOF. We postulate that RV strain will correlate with cardiac MRI (CMR) volumetric data. Methods: Retrospective study of 55 patients s/p TOF repair compared to 40 normal controls. RV longitudinal strain was measured from the standard 4-chamber view and circumferential strain from the short axis slice apical to the RV outflow tract. Using CMR software developed in-house that utilizes a semi-automatic segmentation program, peak strain was identified. Unpaired t test assessed differences between groups and correlation was performed between strain and volumetric data. Results: The predominant lesion was regurgitation in 48 (regurgitant fraction (RF) 43±2%), stenosis in 10 (peak gradient 32±2 mmHg), and mixed in 4. Longitudinal strain was reduced in TOF compared to controls while circumferential strain was preserved (Table 1). Correlations found reduced strain with increasing volumes and decreasing right ventricular ejection fraction (RVEF) (Table 2). Longitudinal:circumferential ratio (L/C) increased with increasing volumes and decreasing RVEF. No relationship was found between RV strain and RF. Conclusions: The relationships between longitudinal and circumferential strain, and the L/C ratio with RV volumes and RVEF suggest that preservation of circumferential strain is important in maintaining RV systolic function. Measurement of RV deformation may provide insight into the RV’s response to volume or pressure overload in TOF, suggesting we should focus on RV mechanical changes rather than RF when managing these patients.
Changes in arm tissue composition with slowly-progressive weight-lifting among women with breast cancer-related lymphedema.
Authors: Xiaochen Zhang, Justin C. Brown, Electra D. Paskett, Babette Zemel, Andrea L. Cheville, KATHRYN H. SCHMITZ
Journal: Journal of Clinical Oncology (2017)

114 Background: We evaluated baseline differences in arm tissue composition (fat mass, lean mass, bone mineral content [BMC] and bone mineral density [BMD]) between the affected and unaffected arms in women with breast cancer-related lymphedema (BRCL). We compared changes in arm tissue composition and self-reported lymphedema symptoms after one-year of weight-lifting vs. usual-care. Methods: We utilized data from the PAL trial that included 141 women with BRCL. Arm tissue composition was quantified using dual-energy x-ray absorptiometry. The severity of lymphedema was quantified using self-report survey. Weight-lifting was performed at community fitness facilities. Results: At baseline, the affected arm had more fat (D= 89.7±21.0g; P &lt; 0.001) and lean mass (D= 149.1±25.3g; P &lt; 0.001), but less BMC (D= -3.2±0.9g; P &lt; 0.001) than the unaffected arm. No difference was observed in BMD. After 12-months of weight-lifting, composition of the affected arm was improved: lean mass (71.2±27.9g; P = 0.01) and BMD (0.01±0.01g; P = 0.02) increased, arm fat percentage decreased (0.01±0.01; P = 0.003). No changes observed in fat mass and BMC. Baseline body mass index and BCRL grade modified the relationship between weight-lifting and tissue composition changes. Increases in lean mass were associated with less severe BCRL symptoms. With every one-percent decrease in arm fat percentage, affected limb volume reduced 13.81mL. Conclusions: Among women with BRCL, affected and unaffected arms differ in tissue composition. These differences may be improved with weight-lifting. Changes in arm tissue composition correlate with improved BCRL symptoms. Investigating the combined effects of exercise and weight-loss on arm tissue composition and BCRL symptoms may provide additional insight to the benefits of lifestyle modification on lymphedema biology. Clinical trial information: NCT00194363.
Laundry detergents and detergent residue after rinsing directly disrupt tight junction barrier integrity in human bronchial epithelial cells
Authors: Ming Wang, Ge Tan, Andrzej Eljaszewicz, Yifan Meng, Paulina Wawrzyniak, Swati Acharya, Can Altunbulakli, Patrick Westermann, Anita Dreher, Liying Yan, Chengshuo Wang, Mubeccel Akdis, Luo Zhang, Kari C. Nadeau, Cezmi A. Akdis
Journal: Journal of Allergy and Clinical Immunology (2018)
Facilitated access to medical specialist care: The novel approach to support informal hospice caregivers—Analysis of caregivers’ needs and satisfaction.
Authors: Janusz Wojtacki, Anna Janowicz, Piotr Krakowiak, Agnieszka Łabuć
Journal: Journal of Clinical Oncology (2018)

11 Background: Real life observations suggest hospice caregiving may result in physical health deterioration of family caregivers; they are less likely to participate in health-related initiatives and frequently don’t benefit from the most optimal medical care. Data reporting caregivers’ medical needs are rather scarce. Methods: The estimation of needs for specialist medical care aimed at family caregivers was carried out based on the activity called Open Day of Health Prophylaxis (ODHP – free consultations with specialists, ultrasound examinations and mammography) held annually at Rev. Eugeniusz Dutkiewicz SAC Hospice, Gdańsk, Poland during three consecutive years (2014 - 2018). In total, 715 medical consultations (median: 3 per caregiver, range: 1 - 6), 172 ultrasound, and 31 mammogram examinations were provided). The level of satisfaction expressed by the ODHP participants was also analyzed. Demographic, medical data, and involvement in the caregiving were analyzed based on consultation cards and questionnaires presented to all ODHP participants (307 total participants). Results: In total, 186 persons replied (60.59%), 103 of them fulfilled study inclusion criteria (currently or within the last 6 months providing personal care of a chronically ill person for minimum 12 hours per week), 82 (79.61%) of responders were women, most of advanced age (median: 67 years; range: 29 - 91). The vast majority (95.31%) estimated ODHP as valuable initiative. According to 52.23% ODHP completely fulfilled caregivers’ needs and expectations, 45.57% were partly satisfied, and for 2.13% the activity did not meet their expectations. The most common reason for dissatisfaction in the response was both lack of communication and access to specialists, as well inability to initiate other diagnostic tests. All responders indicated the expedient nature of ODHP activity. Conclusions: Facilitated access to medical specialists care in is well received form of support for family hospice caregivers. There is indication of a need for systemic solutions to the problems of medical care for long-term caregivers.
Next steps: Incorporating patient-reported outcomes into palliative care referral for people with advanced breast cancer.
Authors: Yun Rose Li, Celine Denise Marquez, Hope S. Rugo, Michael W. Rabow, Laura Esserman
Journal: Journal of Clinical Oncology (2018)

133 Background: Specialty palliative care (SPC) has been shown to improve quality of life, reduce unnecessary health care utilization, reduce overall costs, and decrease mortality in some settings for patients with advanced or metastatic cancer, however only a small proportion are being promptly referred. As interventions that respond to patient reported outcomes (PROs) have been shown to improve symptoms and decrease mortality, we hypothesized that the rates of SPC referral would be increased by documenting, tracking, and presenting PROs for oncology visits to referring oncologists. Methods: Over a period of 2 months, 74 English-speaking established patients seen in an advanced breast cancer clinic with an embedded SPC service were approached and completed the study. All patients filled out the electronic, validated PROMIS and PRO-CTCAE PRO questionnaires in the waiting room using a touch screen tablet. Results were presented to the oncologist during the encounter if the CTCAE severity score exceeded 3 in at least 1 domain. Patient demographics, clinical features and PC referrals or appointments were assessed via chart review. Results: At baseline, 9 (12.2%) patients scored a minimum of “severe” (4/5 or 5/5) in at least 1 of the 3 anxiety domains; 17 (23.0%) had moderate-severe pain; and 27 (32.1%) reported fatigue. At study entry, 25 patients (33.8%) had been referred previously to the SPC service; 19 had actually been seen (76% of referred). Of the 63 (85.1%) patients with sufficient follow-up, 13 (20.6%) reported at least “severe” in &gt;1 CTCAE domains, 6 (46.2%) of whom were previously referred to SPC. For the remaining 7 patients, median PROMIS T-score and PRO-CTCAE maximum severity score were 58.3 and 3.2, respectively; none were referred to SPC during the follow up period. Conclusions: The choice to refer (or not to refer) a patient to SPC is complex and tied to patient specific factors such as coordinating additional visits and fear of end of life conversations. To enable greater access to SPC, alternative referral mechanisms, such as group-based or personalized patient education, or automatic referrals triggered by evidence of need, may be required. #YRL/CDM contributed equally.
Abstract 19174: Bmal1 Deficiency in Myeloid Cells Promotes Hypertension and Hypertension-associated Renal and Vascular Inflammation in Mice
Authors: Mingyu Huo, Danyang Tian, Chi Wai Lau, Hongsong Zhang, Ajay Chawla, Yu Huang, Xiao Yu Tian
Journal: Circulation (2017)

Introduction: The molecular clock plays an essential role in regulating cardiovascular function and immune responses through rhythmic expression of clock-controlled transcripts and their biological...
The Tumor Microenvironment of Nodular Lymphocyte Predominant Hodgkin Lymphoma Is a Unique Immunobiological Entity Distinct from Classical Hodgkin Lymphoma
Authors: Jay Gunawardana, Karolina Bednarska, Soi C Law, Justina Lee, Muhammed Bilal Sabdia, Joshua W.D. Tobin, Simone Birch, Colm Keane, Maher K Gandhi
Journal: Blood (2018)
A common transcriptomic program acquired in the thymus defines tissue residency of MAIT and NKT subsets
Authors: Marion Salou, François Legoux, Jules Gilet, Aurélie Darbois, Anastasia du Halgouet, Ruby Alonso, Wilfrid Richer, Anne-Gaëlle Goubet, Céline Daviaud, Laurie Menger, Emanuele Procopio, Virginie Premel, Olivier Lantz
Journal: The Journal of Experimental Medicine (2018)

Mucosal-associated invariant T (MAIT) cells are abundant T cells with unique specificity for microbial metabolites. MAIT conservation along evolution indicates important functions, but their low frequency in mice has hampered their detailed characterization. Here, we performed the first transcriptomic analysis of murine MAIT cells. MAIT1 (RORγtneg) and MAIT17 (RORγt+) subsets were markedly distinct from mainstream T cells, but quasi-identical to NKT1 and NKT17 subsets. The expression of similar programs was further supported by strong correlations of MAIT and NKT frequencies in various organs. In both mice and humans, MAIT subsets expressed gene signatures associated with tissue residency. Accordingly, parabiosis experiments demonstrated that MAIT and NKT cells are resident in the spleen, liver, and lungs, with LFA1/ICAM1 interactions controlling MAIT1 and NKT1 retention in spleen and liver. The transcriptional program associated with tissue residency was already expressed in thymus, as confirmed by adoptive transfer experiments. Altogether, shared thymic differentiation processes generate "preset" NKT and MAIT subsets with defined effector functions, associated with specific positioning into tissues.
IL-1β Inhibition Reduces Atherosclerotic Inflammation in HIV Infection
Authors: Priscilla Y. Hsue, Danny Li, Yifei Ma, Amorina Ishai, Maura Manion, Matthias Nahrendorf, Peter Ganz, Paul M Ridker, Steven G. Deeks, Ahmed Tawakol
Journal: Journal of the American College of Cardiology (2018)
Differentiation of peripheral nerve sheath tumors in patients with neurofibromatosis type 1 using diffusion-weighted magnetic resonance imaging
Authors: Lennart Well, Johannes Salamon, Michael G Kaul, Said Farschtschi, Jochen Herrmann, Karin I Geier, Christian Hagel, Maximilian Bockhorn, Peter Bannas, Gerhard Adam, Victor F Mautner, Thorsten Derlin
Journal: Neuro-Oncology (2018)

We sought to determine the value of diffusion-weighted (DW) magnetic resonance imaging (MRI) for characterization of benign and malignant peripheral nerve sheath tumors (PNSTs) in patients with neurofibromatosis type 1 (NF1). Twenty-six patients with NF1 and suspicion of malignant transformation of PNSTs were prospectively enrolled and underwent DW MRI at 3T. For a set of benign (n = 55) and malignant (n = 12) PNSTs, functional MRI parameters were derived from both biexponential intravoxel incoherent motion (diffusion coefficient D and perfusion fraction f) and monoexponential data analysis (apparent diffusion coefficients [ADCs]). A panel of morphological MRI features was evaluated using T1- and T2-weighted imaging. Mann–Whitney U-test, Fisher's exact test, and receiver operating characteristic (ROC) analyses were applied to assess the diagnostic accuracy of quantitative and qualitative MRI. Cohen's kappa was used to determine interrater reliability. Malignant PNSTs demonstrated significantly lower diffusivity (P < 0.0001) compared with benign PNSTs. The perfusion fraction f was significantly higher in malignant PNSTs (P < 0.001). In ROC analysis, functional MRI parameters showed high diagnostic accuracy for differentiation of PNSTs (eg, ADCmean, 92% sensitivity with 98% specificity, AUC 0.98; Dmean, 92% sensitivity with 98% specificity, AUC 0.98). By contrast, morphological imaging features had only limited sensitivity (18–94%) and specificity (18–82%) for identification of malignancy. Interrater reliability was higher for monoexponential data analysis. DW imaging shows better diagnostic performance than morphological features and allows accurate differentiation of benign and malignant peripheral nerve sheath tumors in NF1.
Dry eye after whole brain radiation: Analysis from a prospective study.
Authors: Rachel Tobillo, Kevin A. Pearlstein, Zahra Mahbooba, Dominic Himchan Moon, Colette J. Shen, Lawrence Bruce Marks, Bhishamjit S. Chera, Kyle Wang
Journal: Journal of Clinical Oncology (2018)

198 Background: Lacrimal glands (LGs) receive incidental dose of unknown significance in patients undergoing whole brain radiation therapy (WBRT). Median survival following diagnosis of brain metastases is poor, so quality of life is of utmost importance for these patients. We enrolled patients on a prospective observational cohort study with an endpoint of dry eye syndrome, which is not thought to be a toxicity of WBRT. Methods: Patients receiving WBRT for any diagnosis to a total dose of 25 to 40 Gy in 10 to 20 fractions were eligible. Patients received 3D-conformal WBRT using opposed lateral fields covering the skull and C1 or C2 vertebrae. LGs were not prospectively contoured before treatment but were subsequently contoured for dosimetric analysis. Patients completed the single-question Subjective Evaluation of Symptom of Dryness (5-point Likert scale) at baseline, immediately after WBRT (EndRT), 1 month (1M), 3 months (3M), and 6 months (6M). The primary endpoint was change in proportion of patients at 1M experiencing moderate or worse dry eye (defined as symptoms that cause discomfort and interfere with activities). Orbital dose was analyzed as a surrogate for LG dose as LGs were difficult to contour on computed tomography (CT) imaging. Results: 73 enrolled patients were eligible for analysis. There were 69 evaluable patients at EndRT, 55 at 1M, 33 at 3M, and 28 at 6M. Most patients received 30 Gy in 10 fractions. Median bilateral orbit mean dose was 17 Gy. Median bilateral lacrimal mean dose was 25 Gy. Median survival was 8 months. At baseline, 4% of patients had moderate or worse dry eye versus 9% at EndRT, 11% at 1M (1-tailed sign test, p = 0.031), 9% at 3M, and 7% at 6M. No significant relationship was noted between presence of dry eye and CT-contoured lacrimal gland or orbit doses. Conclusions: WBRT appears to cause a small increase in dry eye symptoms. A correlation between dry eye and LG dose was not observed, perhaps due to the overall low rate of toxicity, uncertainty in CT-based contouring of the LGs, set-up variations between planned and delivered doses, and the possibility of non-radiation causes of dry eye. Nonetheless, physicians should be aware of the possible occurrence of dry eye after WBRT, given its potential effects on quality of life.