tbuckley/cabot-search huggingface dataset:
Patients with CD3G mutations reveal a role for human CD3γ in Treg diversity and suppressive function
Authors: Jared H. Rowe, Ottavia M. Delmonte, Sevgi Keles, Brian D. Stadinski, Adam K. Dobbs, Lauren A. Henderson, Yasuhiro Yamazaki, Luis M. Allende, Francisco A. Bonilla, Luis I. Gonzalez-Granado, Seyma Celikbilek Celik, Sukru N. Guner, Hasan Kapakli, Christina Yee, Sung-Yun Pai, Eric S. Huseby, Ismail Reisli, Jose R. Regueiro, Luigi D. Notarangelo
Journal: Blood (2018)
Bioinspired supramolecular engineering of self-assembling immunofibers for high affinity binding of immunoglobulin G
Authors: Yi Li, Lye Lin Lock, Yuzhu Wang, Shih-Hao Ou, David Stern, Arne Schön, Ernesto Freire, Xuankuo Xu, Sanchayita Ghose, Zheng Jian Li, Honggang Cui
Journal: Biomaterials (2018)
Maternal IL-6 during pregnancy can be estimated from newborn brain connectivity and predicts future working memory in offspring
Authors: Marc D. Rudolph, Alice M. Graham, Eric Feczko, Oscar Miranda-Dominguez, Jerod M. Rasmussen, Rahel Nardos, Sonja Entringer, Pathik D. Wadhwa, Claudia Buss, Damien A. Fair
Journal: Nature Neuroscience (2018)
Evaluating the antitumor role of B cells in patients with non-small cell lung cancer.
Authors: Tullia C. Bruno
Journal: Journal of Clinical Oncology (2017)

75 Background: The focus of immunotherapy has been on CD8 and CD4 tumor infiltrating lymphocytes (TILs), however, tumor infiltrating B cells (TIL-Bs) have been reported in tertiary lymphoid structures (TLS) with CD4 TILs, and both TIL-Bs and TLS correlate with NSCLC patient survival. While TIL-Bs have been identified in NSCLC patients, their function in the tumor microenvironment has been understudied with no focus on their role as antigen presenting cells (APCs) and their influence on CD8 and CD4 TILs. We hypothesize that TIL-Bs help generate potent, long-term immune responses against cancer by presenting tumor antigens to CD4 TILs. Methods: We used freshly isolated B cells from NSCLC patient tumor and tumor adjacent tissue to determine TIL-B function. We generated a specific in vitro antigen presentation assay to determine APC function and immunoregulation by TIL-Bs, and we correlated our findings with tumor-free survival. Results: We observed that the total number of B cells at the site of the tumor versus the tumor-adjacent tissue was increased compared to other immune subsets. Further, we observed three types of CD4 TIL responses when TIL-Bs presented autologous tumor antigens. There were activated responder CD4 TILs that proliferated when combined with TIL-Bs alone, which indicates stimulation with endogenous tumor antigens. There were antigen-associated responders that required exogenous autologous tumor lysate to elicit a CD4 TIL response, and there were patient CD4 TILs that did not respond to antigen presentation by TIL-Bs. Within the activated and antigen-associated responders, the TIL-B phenotype influenced the CD4 TIL phenotype; if the TIL-Bs were activated (CD69+CD27+CD21+), the CD4 TILs were T helper (anti-tumor) CD4 T cells and if the TIL-Bs were exhausted (CD69-CD27-CD21-), the CD4 TILs were T regulatory cells (pro-tumor). These data suggest that TIL-Bs influence the phenotype and function of CD4 TILs in NSCLC patient tumors. Conclusions: In conclusion, determining if TIL-Bs are activated or exhausted in NSCLC patients will determine the extent of their anti-tumor function in cancer. Ultimately, results from this study will help predict how to target TIL-B functions in future immunotherapies for NSCLC patients.
Abstract 16917: Unique Small Molecule Metabolites Are Associated With Racial Differences In Heart Failure Death And Hospitalization
Authors: Alanna A Morris, Karan Uppal, Elizabeth Y Chong, Salim Hayek, Andreas Kalogeropoulos, Vasiliki Georgiopoulou, Dean P Jones, Javed Butler, Arshed Quyyumi
Journal: Circulation (2016)

Introduction:  Clinical outcomes for heart failure with reduced ejection fraction (HFrEF) are worse for Black Americans. We sought to determine if unique small molecule metabolites contribute to racial differences in HF outcomes.   Hypothesis:  Small molecule metabolites will contribute to racial differences in HF death and hospitalization.   Methods:  We performed a metabolome wide association study in 225 Blacks and Whites (46.5% Black) with HFrEF enrolled in the Atlanta Cardiomyopathy Consortium. Kaplan-Meier analysis and Cox proportional hazards regression were used to estimate the association of race and small molecule metabolites with a composite primary endpoint of death and HF hospitalization.   Results:  During a median follow-up of 1114 (IQR 710 - 1422) days, the primary endpoint occurred in 176 (78.2%) patients, including 34 (15.1%) deaths and 174 (77.3%) hospitalizations. Black race was associated with a higher risk for the primary endpoint (adjusted HR 1.59, 95% CI 1.03 - 2.46; P=0.03). 86 metabolites were identified to be differentially expressed between Blacks and Whites at false discovery rate=0.2. The metabolite kynurenate (HR=1.03, 95% CI 1.00 - 1.06, P=0.04), and two metabolites tentatively identified as nitronaphthalene (HR=1.03, 95% CI 1.00 - 1.06, P=0.04) and salsolinol (HR=1.03, 95% CI 1.00 - 1.06, P=0.07) were associated with a higher risk of the primary endpoint in the entire cohort. There was a trend towards a race*salsolinol interaction (P=0.06), with Blacks in the highest salsolinol quartile having the highest risk for the primary endpoint, while Whites in the lowest salsolinol quartile had the lowest risk. Race-stratified Cox models confirmed elevated salsolinol levels were associated with increased risk for the primary endpoint in Whites (quartile 4 vs. 1: adjusted HR 3.07, 95% CI 1.18 - 7.96; P=0.02) and Blacks (quartile 4 vs. 1: adjusted HR 2.24, 95% CI 0.93 - 5.40; P=0.07).   Conclusions:  In a HFrEF cohort, we found 86 metabolites differentially expressed between Blacks and Whites. Kynurenate, and metabolites tentatively identified as nitronaphthalene and salsolinol, were associated with a higher risk of death and HF hospitalization, while that identified as salsolinol was associated with differential risk in Blacks and Whites.
Increased cardiac fatty acid oxidation in a mouse model with decreased malonyl-CoA sensitivity of CPT1B
Authors: Michel van Weeghel, Desiree Abdurrachim, Rianne Nederlof, Carmen A Argmann, Riekelt H Houtkooper, Jacob Hagen, Miranda Nabben, Simone Denis, Jolita Ciapaite, Stephen C Kolwicz, Gary D Lopaschuk, Johan Auwerx, Klaas Nicolay, Christine Des Rosiers, Ronald J Wanders, Coert J Zuurbier, Jeanine J Prompers, Sander M Houten
Journal: Cardiovascular Research (2018)

Mitochondrial fatty acid oxidation (FAO) is an important energy provider for cardiac work and changes in cardiac substrate preference are associated with different heart diseases. Carnitine palmitoyltransferase 1B (CPT1B) is thought to perform the rate limiting enzyme step in FAO and is inhibited by malonyl-CoA. The role of CPT1B in cardiac metabolism has been addressed by inhibiting or decreasing CPT1B protein or after modulation of tissue malonyl-CoA metabolism. We assessed the role of CPT1B malonyl-CoA sensitivity in cardiac metabolism. We generated and characterized a knock in mouse model expressing the CPT1BE3A mutant enzyme, which has reduced sensitivity to malonyl-CoA. In isolated perfused hearts, FAO was 1.9-fold higher in Cpt1bE3A/E3A hearts compared with Cpt1bWT/WT hearts. Metabolomic, proteomic and transcriptomic analysis showed increased levels of malonylcarnitine, decreased concentration of CPT1B protein and a small but coordinated downregulation of the mRNA expression of genes involved in FAO in Cpt1bE3A/E3A hearts, all of which aim to limit FAO. In vivo assessment of cardiac function revealed only minor changes, cardiac hypertrophy was absent and histological analysis did not reveal fibrosis. Malonyl-CoA-dependent inhibition of CPT1B plays a crucial role in regulating FAO rate in the heart. Chronic elevation of FAO has a relatively subtle impact on cardiac function at least under baseline conditions.
Plain-language medical vocabulary for precision diagnosis
Authors: Nicole A. Vasilevsky, Erin D. Foster, Mark E. Engelstad, Leigh Carmody, Matt Might, Chip Chambers, Hugh J. S. Dawkins, Janine Lewis, Maria G. Della Rocca, Michelle Snyder, Cornelius F. Boerkoel, Ana Rath, Sharon F. Terry, Alastair Kent, Beverly Searle, Gareth Baynam, Erik Jones, Pam Gavin, Michael Bamshad, Jessica Chong, Tudor Groza, David Adams, Adam C. Resnick, Allison P. Heath, Chris Mungall, Ingrid A. Holm, Kayli Rageth, Catherine A. Brownstein, Kent Shefchek, Julie A. McMurry, Peter N. Robinson, Sebastian Köhler, Melissa A. Haendel
Journal: Nature Genetics (2018)
The Vasculature in Prediabetes
Authors: David H. Wasserman, Thomas J. Wang, Nancy J. Brown
Journal: Circulation Research (2018)

The frequency of prediabetes is increasing as the prevalence of obesity rises worldwide. In prediabetes, hyperglycemia, insulin resistance, and inflammation and metabolic derangements associated with concomitant obesity cause endothelial vasodilator and fibrinolytic dysfunction, leading to increased risk of cardiovascular and renal disease. Importantly, the microvasculature affects insulin sensitivity by affecting the delivery of insulin and glucose to skeletal muscle; thus, endothelial dysfunction and extracellular matrix remodeling promote the progression from prediabetes to diabetes mellitus. Weight loss is the mainstay of treatment in prediabetes, but therapies that improved endothelial function and vasodilation may not only prevent cardiovascular disease but also slow progression to diabetes mellitus.
Clinicopathological characteristics and HER2 status in metastatic colorectal cancer patients: Results of a diagnostic model development study.
Authors: Andrea Sartore-Bianchi, Alessio Amatu, Luca Porcu, Silvia Ghezzi, Sara Lonardi, Francesca Bergamo, Erica Francesca Bonazzina, Gianluca Mauri, Chiara Cremolini, Fortunato Ciardiello, Emanuele Valtorta, Mauro Truini, Cosimo Martino, Silvia Marsoni, Federica Di Nicolantonio, Giulia Siravegna, Alberto Bardelli, Livio Trusolino, Valter Torri, Salvatore Siena
Journal: Journal of Clinical Oncology (2018)

581 Background: We have reported with the HERACLES Trial that HER2 amplification is a clinically relevant genetic alteration in metastatic colorectal cancer (mCRC). With present study, we aim to develop and internally validate a new diagnostic model for HER2 status in patients with mCRC based on clinicopathological characteristics to improve selection for HER2-targeted therapies and to refine negative selection for EGFR-targeted agents. Methods: Patients with KRAS exon 2 WT mCRC underwent molecular screening of HER2 according to HERACLES criteria (immunohistochemistry 3+ or 2+ in equal or more than 50% of cells, confirmed by FISH) for enrollment in HERACLES clinical trials with HER2-targeted therapies. All HER2-positive cases and a fraction of negative consecutive cases were annotated with clinical and pathological variables. A multivariable logistic regression model with a linear combination of all clinical and pathological characteristics as predictors was fitted to the complete set of data. A regression modeling strategy was applied to the full model to identify predictors explaining the bulk of HER2 amplification. Results: From August 2012 to June 2017, a total of 80 HER2-positive mCRC cases were detected out of 1355 screened patients. The large majority of HER2-positive primary tumors appeared to be left colon- or rectal-sided (88.0%). None of the relevant clinicopathological features explained the bulk of HER2 amplification, even though trends were observed for sidedness (left colon and rectal &gt; proximal, OR 1.75, 95% CI 0.76-4.16), tumour grading (high &gt; low, OR 2.21, 95% CI 0.19-26.38), and metastatic burden (high &gt; low, OR 1.29, 95% IC 0.94-1.77). In a secondary analysis, patients with HER2-amplified mCRC who received treatment with anti-EGFR agents (n = 64) showed poorer outcome (objective response rate: 30% vs 55%, p = 0.044 and progression-free survival: 5.8 months vs 7 months, p = 0.056). Conclusions: Testing for HER2 should be offered to all patients with mCRC since it is unlikely to predict the occurrence of this biomarker based on main clinicopathological features. Patients with HER2-amplified mCRC are less likely to respond to anti-EGFR therapy.
Abstract 16230: Fenestration in the Fontan Circulation Secures Circulatory Reserve~Potential for Chronic Cardio-protective Strategy~
Authors: Hirofumi Saiki, Seiki Kuwata, Clara Kurishima, Yoichi Iwamoto, Hirotaka Ishido, Satoshi Masutani, Hideaki Senzaki
Journal: Circulation (2016)

Background: Fontan patients are increasingly subjected to advanced heart failure therapies due to end organ failure, which stems from Fontan specific hemodynamics. Since fenestrated Fontan (FF) pro...
Longitudinal Associations Among Bullying by Peers, Disordered Eating Behavior, and Symptoms of Depression During Adolescence
Authors: Kirsty S. Lee, Tracy Vaillancourt
Journal: JAMA Psychiatry (2018)

Bullying by peers has been associated with disordered eating behavior and symptoms of depression among adolescents as both an antecedent and an outcome. Identification of the temporal pattern of associations among bullying by peers, disordered eating behavior, and depression in adolescence is needed for the optimal targeting of intervention and prevention.To assess the concurrent and longitudinal associations among bullying by peers, disordered eating behavior, and symptoms of depression using a cascade model that controlled for within-time and across-time (ie, stability paths) associations while examining cross-lag effects.In this 5-year longitudinal cohort study, 612 participants of the McMaster Teen Study were included. This ongoing Canadian study examines the associations among bullying, mental health, and educational outcomes. Data collection began in 2008 when students were in grade 5 (10 years of age) and have since been collected annually. Data analysis was performed between August 20 and October 18, 2017.Bullying by peers was assessed in grades 7 to 11 using a composite measure of 5 items.Disordered eating behavior was assessed in grades 7 to 11 using the Short Screen for Eating Disorders, and depressive symptoms were assessed in grades 7 to 11 using the Behavior Assessment System for Children-Second Edition.The 612 students included in the analytic sample had a mean age (SD) of 13.03 (0.38) years in grade 7; 331 (54.1%) were girls and 392 (71.1%) were white. Bullying by peers was concurrently associated with disordered eating behavior and depressive symptoms at every time point during the 5-year period (r range [SE], 0.15-0.48 [0.04-0.08]; P < .01). Disordered eating behavior was associated longitudinally with depressive symptoms at every time point (β range [SE], 0.14-0.19 [0.06-0.08]; P < .02) and bullying by peers at 2 time points (β range [SE], 0.12-0.22 [0.06-0.07]; P < .04) in girls and boys.Bullying by peers was proximally associated with multiple psychopathologic symptoms, whereas symptoms of disordered eating behavior were a key risk factor for future depressive symptoms and bullying by peers. Interventions aimed at reducing problematic eating behavior in adolescents may attenuate the risk of future depressive symptoms and relational problems.
Social transmission bias and the cultural evolution of folk-economic beliefs
Authors: David Hirshleifer, Siew Hong Teoh
Journal: Behavioral and Brain Sciences (2018)

Abstract Evolved dispositions influence, but do not determine, how people think about economic problems. The evolutionary cognitive approach offers important insights but underweights the social transmission of ideas as a level of explanation. The need for a social explanation for the evolution of economic attitudes is evidenced, for example, by immense variations in folk-economic beliefs over time and across individuals.
Pulmonary alveolar proteinosis and <i>Mycobacterium abscessus</i> lung infection related to ruxolitinib after allogeneic stem cell transplantation
Authors: Hélène Salvator, Enora Berti, Emilie Catherinot, Elisabeth Rivaud, Alexandre Chabrol, Stephanie Nguyen, Leila Zemoura, Emilie Cardot, Colas Tcherakian, Louis-Jean Couderc
Journal: European Respiratory Journal (2018)

Non-infectious pulmonary complications are frequent after allogeneic haematopoietic stem cell transplantation (HSCT). They mainly comprise bronchiolitis obliterans and interstitial pneumonia in the setting of chronic graft- versus -host disease (cGVHD) [1]. Ruxolitinib may induce pulmonary alveolar proteinosis and favour respiratory non-tuberculous mycobacterial infections <http://ow.ly/bTXn30jogC8> The authors thank all the members of Foch Hospital Lung Immune Deficiencies study group for their dedication and their daily work with patients. Thoracic surgery: Alain Chapelier, Edouard Sage, Pierre Bonnette, and Philippe Puyo; intensive care unit: François Parquin and Gregoire Trebbia; radiology: François Mellot, Axel Guth, Fabrice Staub and Marie-Laure Chabi; microbiology: Eric Farfour and Pierre Cahen.
Abstract 193: Hemophagocytic lymphohistiocytosis following kawasaki disease:Differential Diagnosis in IVIG Refractory Kawasaki Disease
Authors: Hyun Ok Jun, Eun Kyung Cho, Jeong Jin Yu, So Yeon Kang, Chang Deok Seo, Jae Suk Baek, Young-Hwue Kim, Jae-Kon Ko, Ho-Joon Im
Journal: Circulation (2015)

Introduction: Hemophagocytic lymphohistiocytosis(HLH) is a systemic inflammatory disorder characterized by uncontrolled histiocytic proliferation, hemophagocytosis and up-regulation of inflammatory cytokines. Thus, both HLH and Kawasaki disease(KD) are characterized by prolonged fever, and are diagnosed by a clinical and laboratory scoring system, concurrent manifestation of HLH and KD has been described in the literature. We describe two cases of children who diagnosed as KD initially, but after intravenous gamma globulin(IVIG) failed to produce clinical response, were found to have HLH. Case report: A 3-year-old boy who had previous KD history 5 months ago was admitted for 9day fever and skin rash. His symptoms were fulfilled KD criteria, and echocardiography showed dilated right coronary artery of 4.2mm. He was treated with 2 cycles of IVIG until fever subsided. However, 2 days later, he got fever again and cytopenia(Hb&lt;9.0), hypertriglyceridemia, high level of ferritin was shown and had splenomegaly on physical examination. In the suspicion of HLH, bone marrow biopsy was done and revealed hemophagocytosis, consistent with HLH. A second case of 11-month-old boy admitted for 8-day fever with Kawasaki feature. Although, he showed incomplete feature(fever, skin rash, conjunctival injection, cervical lymphadenopathy), echocardiography showed dilated left main coronary artery(3.5mm) and treated with IVIG. However, 2days after IVIG administration, he was still pyrexial. The laboratory findings fulfilled 5 diagnostic criteria of HLH; bicytopenia(anemia, thrombocytopenia), hypofibrinogenemia, hyperferritinemia, hemophagocytosis in bone marrow, raised level of soluble IL-2 receptor. In both cases, the patients treated according to the HLH protocol 2004, and after that clinical symptoms and laboratory findings were improved. Several causes of febrile illness, EBV, CMV, rubella, parvo-viral infection, for example, were excluded. Comment: There is considerable overlap between the clinical syndromes of KD and HLH and early recognition and treatment of these two disease entity is imperative to avoid fatal outcomes in severe cases. Thus, these should both be considered and excluded in any child with unremitting fever and rash.
Abstract P66: Differences in Chest Compressions Provided to Male and Female Victims of Out-of-Hospital Cardiac Arrest
Authors: Andre Kemeny, Annemarie Silver, Weilun Quan, Gary Freeman, Charles Babbs
Journal: Circulation (2008)

Background: Prehospital healthcare providers may fear that they will injure patients while performing manual chest compressions (CC). The provider’s perception of a patient’s fragility may influence the aggressiveness with which he/she performs CC. As a consequence, EMS personnel may provide CC of differing forcefulness when treating male versus female patients. The objective of the present study was to compare the depth of CC provided to male and female patients. A secondary objective was to determine whether there were gender differences in delays and interruptions in CC. Methods: Data were recorded from the treatment of 203 out-of-hospital cardiac arrest patients (60 female and 143 male) using ZOLL AED Plus devices, which are capable of recording CC depth, shock timing, and CC timing. Mood’s median statistical test was used to compare the proportions of females vs. males receiving less than median CC depth during pre-shock and post-shock sets of CC, less than median CC start delay (time to CC after pad placement), and less than median pre-shock and post-shock CC interruption times. A total of 420 shocks (n=307 for male, n=103 for female) were included in the analysis. Results: 68% females vs. 45% of males received less than the median pre-shock CC depth of 1.74 in (p=0.002). 58% females vs. 47% of males received less than the median post-shock CC depth of 1.77 in (p=0.07). For delay in starting CC after pad placement, 65% of females vs. 45% of males had below the median delay of 12.95 sec (p&lt;0.0001) and for CC interruption time prior to a shock, 61% females vs. 46% of males had below the median interruption time of 22.87 sec (p=0.009). Conclusions: Prehospital healthcare providers are more likely to perform CC of lower depth when treating female compared with male patients, perhaps due to fear of injuring female patients. Although lower depth of CC could negatively impact resuscitation outcome for females, shorter delays in beginning CC and shorter pre-shock interruptions could alternatively improve outcome for female patients.
Hepatitis B virus evades innate immunity of hepatocytes but activates cytokine production by macrophages
Authors: Xiaoming Cheng, Yuchen Xia, Elisavet Serti, Peter Daniel Block, Michelle Chung, Kazuaki Chayama, Barbara Rehermann, T. Jake Liang
Journal: Hepatology (2017)

Hepatitis B virus (HBV) infects hepatocytes specifically and causes immune-mediated liver damage. How HBV interacts with the innate immunity at the early phase of infection, either with hepatocytes or other cells in the liver, remains controversial. To address this question, we utilized various human cell-culture models and humanized Alb-uPA/SCID mice. All these models were unable to mount an interferon (IFN) response despite robust HBV replication. To elucidate the mechanisms involved in the lack of IFN response, we examined whether HBV actively inhibits innate immune functions of hepatocytes. By treating HBV-infected cells with known inducers of the IFN signaling pathway, we observed no alteration of either sensing or downstream IFN response by HBV. We showed that the DNA innate sensing pathways are poorly active in hepatocytes, consistent with muted innate immune recognition of HBV. Upon exposure to high-level HBV, human macrophages could be activated with increased inflammatory cytokine expressions.HBV behaves like a "stealth" virus and is not sensed by, nor actively interferes with, the intrinsic innate immunity of infected hepatocytes. Macrophages are capable of sensing HBV, but require exposure to high HBV titers, potentially explaining the long "window period" during acute infection and HBV's propensity to chronic infection. (Hepatology 2017;66:1779-1793).