tbuckley/cabot-search huggingface dataset:
Chemokine Receptor 4 Expression in Primary Sjögren’s Syndrome
Authors: Wojciech Cytawa, Stefan Kircher, Andreas Schirbel, Takahiro Shirai, Kazuhito Fukushima, Andreas K. Buck, Hans-Jürgen Wester, Constantin Lapa
Journal: Clinical Nuclear Medicine (2018)

Ga-pentixafor is a novel radioligand of C-X-C motif chemokine receptor 4. A 55-year-old woman with a history of primary Sjögren's syndrome underwent Ga-pentixafor PET/CT for staging of lymphoma originating from mucosa-associated lymphoid tissue. Whereas no lymphoma manifestation could be detected, imaging revealed bilateral intense radiotracer uptake in both parotid and submandibular salivary glands, consistent with inflammatory cell infiltration.
Prenatal antidepressant use and risk of attention-deficit/hyperactivity disorder in offspring
Authors: Kenneth K C Man, Esther W Chan, Patrick Ip, David Coghill, Emily Simonoff, Phyllis K L Chan, Wallis C Y Lau, Martijn J Schuemie, Miriam C J M Sturkenboom, Ian C K Wong
Journal: BMJ (2017)
Abstract 20753: Cardiosphere-Derived Cell Exosomes Enhance Macrophage Efferocytosis to Reduce Infarct Size Following Ischemia/Reperfusion Injury
Authors: Geoffrey de Couto, Ervin Jaghatspanyan, Matthew De Berge, Edward Thorp, Eduardo Marbán
Journal: Circulation (2017)

Introduction: Cardiosphere-derived cells (CDCs) and CDC exosomes (CDCexo) are cardioprotective against ischemia/reperfusion (I/R) injury if delivered within 20-30 mins of reperfusion (Kanazawa et a...
Protection of glucotoxicity by a tripeptide derivative of α‐melanocyte‐stimulating hormone in human epidermal keratinocytes
Authors: P. Gkogkolou, M. Sarna, T. Sarna, R. Paus, T.A. Luger, M. Böhm
Journal: British Journal of Dermatology (2018)

Chronic skin ulcers are a major complication and a therapeutic challenge in patients with diabetes mellitus. Glucose-induced accumulation of reactive oxygen species (ROS) is considered to be an important pathogenetic factor in diabetes.To characterize the impact of high glucose (HG) on normal human keratinocytes (NHKs) and examine if Lys-d-Pro-Thr (KdPT), a tripeptide derived from α-melanocyte-stimulating-hormone, has protective effects.We investigated the key functions of NHKs under HG conditions with or without KdPT in vitro as well as ex vivo employing a skin organ culture model.HG impaired metabolic activity, cell proliferation, viability and migration of NHKs. As shown by atomic force microscopy HG altered the biophysical properties of NHKs, i.e. cell size and elasticity. Glucotoxicity in NHKs was paralleled by the induction of intracellular ROS and endoplasmic reticulum stress. KdPT attenuated HG-induced oxidative stress and antagonized the effects of glucose on cell viability, metabolic activity and migration. Importantly, KdPT also antagonized the suppressive effect of HG on epidermal migration in wounded human skin organ cultures.Our findings highlight a novel effect of KdPT that could be exploited for the future therapy of diabetic skin ulcers.
Abstract 14771: High Burden of Ventricular Premature Complex in Addition to Age and Diastolic Dysfunction are Correlated With Recovery of Neurohormonal Cardiac Dysfunction After Ablation
Authors: Nobuhiko Makino, Yasuyuki Egami, Akihiro Tanaka, Naotaka Okamoto, Naoki Mori, Daisuke Nakamura, Masamichi Yano, Ryu Shutta, Masami Nishino, Jun Tanouchi
Journal: Circulation (2016)

Background: Frequent premature ventricular complexes (PVC) occasionally cause cardiomyopathy and, in some cases, cardiac dysfunction can recover after catheter ablation for PVC. The pathophysiology of these cardiomyopathies remains unknown, but hypotheses mainly include ventricular dyssynchrony resulting in hemodynamic disturbances and abnormalities in calcium handling and oxygen consumption.However, there are few reports on recovery of neurohormonal dysfunction after ablation for frequent PVC Aim: In this study, we investigated which factors were correlated with the recovery of neurohormonal cardiac dysfunction after ablation for PVC Methods: We enrolled the consecutive patients who underwent successful ablation for frequent PVC. We divided our patients into the two group: the recovery (R) group whose brain natriuretic peptide (BNP) were decreased more than 50pg/ml after ablation as compared to the value before ablation and non-recovery (NR) group whose BNP were decreased less than 50pg/ml after ablation...
Abstract 12196: Optic Atrophy 1 Deficiency in Skeletal Muscle Results in Progressive Mitochondrial Dysfunction, but Prevents Age-Induced Obesity and Glucose Intolerance
Authors: Renata Pereira, Zhonggang Li, Karen Oliveira, Karla Pires, E. Dale Abel
Journal: Circulation (2014)

Mitochondrial dysfunction develops in skeletal muscle with aging and may contribute to insulin resistance, which increases cardiovascular risk. A link between skeletal muscle insulin resistance and perturbed mitochondrial fusion and fission has been suggested but not proven. Optic Atrophy 1 (OPA1) is an inner mitochondrial membrane protein that plays a fundamental role in mitochondrial fusion, quality control and respiratory function. OPA1 levels are reduced in muscle from elderly subjects; however, the specific roles of OPA1 in the aging muscle have not been studied. We, therefore, generated a mouse model with inducible deletion of the OPA1 gene in skeletal muscle of adult C57Bl6 mice, by crossing OPA1 floxed mice with HSA-Cre (ERT2) mice (KO). Four-week-old KO and wild-type (WT) mice were treated with tamoxifen for 5 days to induce recombination, resulting in a 60% reduction in OPA1 protein levels 8 weeks after treatment (12-wk-old mice). OPA1 deficiency resulted in altered mitochondrial cristae morphology, with preserved maximally stimulated mitochondria respirations in soleus and reduced ATP synthesis rates in KO mice, 8 weeks after recombination (12-wk-old mice). At 20 weeks, mitochondrial respiration and ATP synthesis were decreased in KO mice, concomitantly with increased AMPK and eIF2 alpha activation. Body weight was reduced in 12 and 20-week old KO mice relative to WT. At forty-weeks, body weight was increased by 40% in WT mice vs. 15% in KO mice. This increase in body weight occurred on the basis of increased fat mass (70% in WT vs. 30% in KO). Lean mass was reduced by 30% in WT mice, which was attenuated in KO mice (~10%). Glucose tolerance tests were similar between WT and KO mice at 12 and 20 weeks of age; however, 40-wk-old WT mice had severe glucose intolerance, which was prevented in KO mice. Interestingly, KO mice had a100-fold increase in FGF21 mRNA levels in muscle compared to WT mice. These data reveal that OPA1 is critical for maintaining skeletal muscle mitochondrial function in the adult muscle and suggest that reducing OPA1 levels activates signaling pathways that retard age-induced obesity and glucose intolerance.
Randomised placebo-controlled trial of dietary glutamine supplements for postinfectious irritable bowel syndrome
Authors: QiQi Zhou, Meghan L Verne, Jeremy Z Fields, John J Lefante, Sarpreet Basra, Habeeb Salameh, G Nicholas Verne
Journal: Gut (2018)

More effective treatments are needed for patients with postinfectious, diarrhoea-predominant, irritable bowel syndrome (IBS-D). Accordingly, we conducted a randomised, double-blind, placebo-controlled, 8-week-long trial to assess the efficacy and safety of oral glutamine therapy in patients who developed IBS-D with increased intestinal permeability following an enteric infection.
One-Year Outcomes After Transapical Echocardiography-Guided Mitral Valve Repair
Authors: Andrea Colli, Erica Manzan, Laura Besola, Eleonora Bizzotto, Alessandro Fiocco, Fabio Zucchetta, Lorenzo Bagozzi, Roberto Bellu, Gentian Denas, Demetrio Pittarello, Gino Gerosa
Journal: Circulation (2018)
Diagnostic 123I Whole Body Scan Prior to Ablation of Thyroid Remnant in Patients With Papillary Thyroid Cancer
Authors: Hong Song, Camila Mosci, Haruko Akatsu, Marina Basina, Chrysoula Dosiou, Andrei Iagaru
Journal: Clinical Nuclear Medicine (2018)

Objectives The use of 123 I whole body scintigraphy (WBS) before 131 I radioiodine ablation (RIA) of the post-surgical thyroid remnant in patients with papillary thyroid cancer (PTC) remains debated. The American Thyroid Association’s guidelines state that WBS may be useful before RIA (rating C—expert opinion). Some institutions do not use 123 I WBS before RIA in their routine clinical protocol. We were therefore prompted to evaluate the impact of 123 I WBS prior to ablation of thyroid remnant in patients with PTC. Methods We reviewed data from 152 consecutive patients with PTC who had total thyroidectomy and were referred for RIA between August 2007 and February 2009 at our institution. The group included 107 women and 45 men, 13–82 years old (mean ± SD: 45.5 ± 18.3). Three endocrinologists blinded to the results of the 123 I WBS reviewed patients’ data including sex, age, pathology, thyroglobulin (Tg) level, anti-Tg antibodies, thyroid stimulating hormone (TSH) level and ultrasound results. Each endocrinologist then returned a form with the recommended 131 I dose for each participant, according to the following rules: 50–75 mCi (remnant ablation), 75–125 mCi (lymph nodes metastases), 150 mCi (lung metastases), and 200 mCi (bone metastases). We compared their recommended doses with the actual 131 I doses prescribed after the pre-therapy 123 I WBS. Results All three endocrinologists recommended the same dose in 98.7% of the cases. The dose prescribed by the endocrinologists matched the dose administered after analyzing the 123 I WBS in 77 patients (51%). However, for 46 patients (30%) the endocrinologists would have given a lower dose, for 18 patients (12%) a higher dose than that administered based on the results of the 123 I WBS, while 11 patients (7%) would have been treated unnecessarily (5/11 had no 123 I uptake and 6/11 had 123 I uptake in the breasts). Conclusions Our study suggests a significant role of the pre-therapy 123 I WBS in PTC patients referred for 131 I ablation post-thyroidectomy. The actual 131 I dose that was administered based on the 123 I WBS differed from the dose recommended in the absence of the 123 I WBS in 49% of the cases.
Abstract 16592: Endothelial Cell Inhibitors, Including Plasminogen Activator Inhibitor 1, Form a Complex With Factor XIa Blocking Its Activity and Inducing the Clearance, Internalization and Degradation of Factor XIa
Authors: Cristina Puy, Anh Ngo, András Gruber, David Gailani, Owen J McCarty
Journal: Circulation (2017)

Introduction: The activation of coagulation factor (F) XI by activated (a) coagulation FXII is a prothrombotic process. The endothelium is known to play an antithrombotic role by preventing thrombin generation and platelet activation. However, it is unknown whether the anticoagulant role of the endothelium includes regulation of the activity of FXIa. Hypothesis: Endothelial cells express anticoagulant properties that specifically block the activity of FXIa. Methods: To measure activation of FXI or prekallikrein (PK) bound to washed platelets or human umbilical vein endothelial cells (HUVECs) by FXIIa or FXIa or kallikrein activity, we performed a chromogenic assay. To detect FXIa-inhibitor complexes in either the supernatant (SN) or cell lysate (CL), HUVECs were exposed to FXIa for 2 hours at 4° C, washed and lysed, followed by immunoprecipitation and western blot using an anti- FXIa catalytic domain. To assess FXIa binding to and internalization by HUVECs, cells were exposed to FXIa at 4° C, washed and t...
Neoadjuvant chemotherapy with dose-dense doxorubicin, cisplatin, and paclitaxel in patients with early triple-negative breast cancer (TNBC).
Authors: Mona Frolova, Ekaterina Ignatova, Elena Glazkova, Alexander Petrovsky, Sergei Tjulandin
Journal: Journal of Clinical Oncology (2015)

1074 Background: TNBC is characterized by aggressive behavior and poor prognosis. It has been shown that achievement of pathological complete regression (pCR) after neoadjuvant chemotherapy improved survival of patients (pts) with TNBC. Rates of pCR with standard antracycline- and taxanebased chemotherapy regimens don’t exceed 20-27%. There are strong phenotypic and molecular similarities between BRCA1-related breast cancers and triple-negative sporadic tumors. Markers of BRCA1-dysfunction may predispose sensitivity to specific agents such as platinum salts. We performed a prospective trial to evaluate efficacy of dose-dense schedule of doxorubicin, cisplatin and paclitaxel in correlation with BRCA1-dysfunction in pts with early TNBC (NCT01672671). Methods: Pts with early TNBC (cT1-2N0-1M0) were treated with doxorubicin 25 mg/m2 iv weekly, cisplatin 30 mg/m2 iv weekly and paclitaxel 100 mg/m2 iv weekly for planned 8 weeks with G-CSF 300 mcg 2-4 days followed by surgery. Pathologic response was assessed in correlation with BRCA1-dysfunction in 17 pts. Results: Forty one pts were included in the study. Median agewas 44 years (23-72), 45% of pts had tumor Grade 3, Ki67 was > 20% in 95% of cases. Forty pts completed chemotherapy (median treatment duration 8,9 weeks) and underwent surgery. Twenty-six pts (65%) achieved pCR. With median follow-up of 19,7 months, 3 pts had a disease progression and 2 pt died (one from disease progression and one from pulmonary embolism after 6 injections of chemotherapy). 1-year DFS was 95,1% and OS was 97,5%. The dose-limiting toxicities were neutropenia (53.7% grade 3-4) and mucositis (19.5% grade 3). In 8 pts treatment was discontinued early due to toxicity. Somatic BRCA1 5382insC mutation correlated with achievement of pCR (p = 0.004). All pts with somatic 185delAG and C61G mutations had residual disease (p = 0,2 and 0,2, accordingly). Conclusions: Dose-dense doxorubicin, cisplatin and paclitaxel regimen shows high activity as neoadjuvant treatment of early TNBC with acceptable toxicity. Somatic BRCA1 mutations may determine different responses to platinum-based chemotherapy. Clinical trial information: NCT01672671.
Elaborating the role of reflection and individual differences in the study of folk-economic beliefs
Authors: Kevin Arceneaux
Journal: Behavioral and Brain Sciences (2018)

Abstract Intuitions guide decision-making, and looking to the evolutionary history of humans illuminates why some behavioral responses are more intuitive than others. Yet a place remains for cognitive processes to second-guess intuitive responses – that is, to be reflective – and individual differences abound in automatic, intuitive processing as well.
Biological determinants of health disparities in multiple myeloma
Authors: Cheryl Jacobs Smith, Stefan Ambs, Ola Landgren
Journal: Blood Cancer Journal (2018)

Abstract Multiple myeloma is a rare plasma cell cancer, and incidence rates among patients of African descent are about twice those among patients of European descent. Rates of multiple myeloma vary among different populations, but the reasons for the racial disparities in multiple myeloma are largely unknown. Epidemiology has identified risk factors for multiple myeloma including race, advanced age, gender, family history, and exposure to different genetic toxins including radiation. Race and ancestry play a large role in predicting the risk for multiple myeloma, yet there exists a paucity of literature that explores the molecular contribution of race and ancestry to disease. In this review, we describe the relevant literature that describes the observed racial differences according to distinct tumor immunobiological and ancestral differences in populations.
Hypomorphic caspase activation and recruitment domain 11 (CARD11) mutations associated with diverse immunologic phenotypes with or without atopic disease
Authors: Batsukh Dorjbal, Jeffrey R. Stinson, Chi A. Ma, Michael A. Weinreich, Bahar Miraghazadeh, Julia M. Hartberger, Stefanie Frey-Jakobs, Stephan Weidinger, Lena Moebus, Andre Franke, Alejandro A. Schäffer, Alla Bulashevska, Sebastian Fuchs, Stephan Ehl, Sandhya Limaye, Peter D. Arkwright, Tracy A. Briggs, Claire Langley, Claire Bethune, Andrew F. Whyte, Hana Alachkar, Sergey Nejentsev, Thomas DiMaggio, Celeste G. Nelson, Kelly D. Stone, Martha Nason, Erica H. Brittain, Andrew J. Oler, Daniel P. Veltri, T. Ronan Leahy, Niall Conlon, Maria C. Poli, Arturo Borzutzky, Jeffrey I. Cohen, Joie Davis, Michele P. Lambert, Neil Romberg, Kathleen E. Sullivan, Kenneth Paris, Alexandra F. Freeman, Laura Lucas, Shanmuganathan Chandrakasan, Sinisa Savic, Sophie Hambleton, Smita Y. Patel, Michael B. Jordan, Amy Theos, Jeffrey Lebensburger, T. Prescott Atkinson, Troy R. Torgerson, Ivan K. Chinn, Joshua D. Milner, Bodo Grimbacher, Matthew C. Cook, Andrew L. Snow
Journal: Journal of Allergy and Clinical Immunology (2018)
Comparison of sarcopenia and cachexia in men with chronic heart failure: results from the Studies Investigating Co‐morbidities Aggravating Heart Failure (SICA‐HF)
Authors: Amir Emami, Masakazu Saitoh, Miroslava Valentova, Anja Sandek, Ruben Evertz, Nicole Ebner, Goran Loncar, Jochen Springer, Wolfram Doehner, Mitja Lainscak, Gerd Hasenfuß, Stefan D. Anker, Stephan von Haehling
Journal: European Journal of Heart Failure (2018)
Abstract 17626: Myoscape, a Novel Member of the Stripak Complex, Controls Contractile Function and Hypertrophy in vitro and in vivo via Modulation of Calcineurin Nfat Activity and its Interaction With Pp2a
Authors: Matthias Eden, Philipp Doldi, Christin Tannert, Maxime Branchereau, Pauline Marck, Christophe Heymes, Frey Norbert
Journal: Circulation (2016)

Alterations in cardiomyocyte calcium cycling have been shown to play a major role in the pathophysiology of contractile dysfunction, cardiomyocyte hypertrophy and heart failure. The mammalian Stria...
HER2/EGFR–AKT Signaling Switches TGFβ from Inhibiting Cell Proliferation to Promoting Cell Migration in Breast Cancer
Authors: Fei Huang, Qiaoni Shi, Yuzhen Li, Linlin Xu, Chi Xu, Fenfang Chen, Hai Wang, Hongwei Liao, Zai Chang, Fang Liu, Xiang H.-F. Zhang, Xin-Hua Feng, Jing-Dong J. Han, Shiwen Luo, Ye-Guang Chen
Journal: Cancer Research (2018)

TGFβ signaling inhibits cell proliferation to block cancer initiation, yet it also enhances metastasis to promote malignancy during breast cancer development. The mechanisms underlying these differential effects are still unclear. Here, we report that HER2/EGFR signaling switches TGFβ function in breast cancer cells from antiproliferation to cancer promotion. Inhibition of HER2/EGFR activity attenuated TGFβ-induced epithelial-mesenchymal transition and migration but enhanced the antiproliferative activity of TGFβ. Activation of HER2/EGFR induced phosphorylation of Smad3 at Ser208 of the linker region through AKT, which promoted the nuclear accumulation of Smad3 and subsequent expression of the genes related to EMT and cell migration. In contrast, HER2/EGFR signaling had no effects on the nuclear localization of Smad2. Knockdown of Smad3, but not Smad2, blocked TGFβ-induced breast cancer cell migration. We observed a positive correlation between the nuclear localization of Smad3 and HER2 activation in advanced human breast cancers. Our results demonstrate a key role for HER2/EGFR in differential regulation of Smad3 activity to shift TGFβ function from antitumorigenic to protumorigenic during breast cancer development.Significance: TGFβ signaling can shift from inhibiting to promoting breast cancer development via HER2/EGFR AKT-mediated phosphorylation of Smad3 at S208, enhancing its nuclear accumulation and upregulation of EMT-related genes.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/21/6073/F1.large.jpg Cancer Res; 78(21); 6073-85. ©2018 AACR.
Sales of energy drinks to children to be banned in England under government plan
Authors: Gareth Iacobucci
Journal: BMJ (2018)

The UK government has proposed banning the sale of energy drinks in England to anyone under the age 18 amid growing fears about their effects on children’s health.

A public consultation launched on Thursday 30 August sets out plans to make it illegal for retailers to sell drinks containing high levels of sugar and caffeine to children, given their links to obesity, toothy decay, and other health problems.1 The ban would apply to drinks containing 150 mg or more of caffeine per litre.

The consultation is the latest phase of the government’s childhood obesity plan, which set out a …
Combining surgery and immunotherapy: turning an immunosuppressive effect into a therapeutic opportunity
Authors: Orneala Bakos, Christine Lawson, Samuel Rouleau, Lee-Hwa Tai
Journal: Journal for ImmunoTherapy of Cancer (2018)

<h3>Background</h3> Cancer surgery is necessary and life-saving. However, the majority of patients develop postoperative recurrence and metastasis, which are the main causes of cancer-related deaths. The postoperative stress response encompasses a broad set of physiological changes that have evolved to safeguard the host following major tissue trauma. These stress responses, however, intersect with cellular mediators and signaling pathways that contribute to cancer proliferation. <h3>Main</h3> Previous descriptive and emerging mechanistic studies suggest that the surgery-induced prometastatic effect is linked to impairment of both innate and adaptive immunity. Existing studies that combine surgery and immunotherapies have revealed that this combination strategy is not straightforward and patients have experienced both therapeutic benefit and drawbacks. This review will specifically assess the immunological pathways that are disrupted by oncologic surgical stress and provide suggestions for rationally combining cancer surgery with immunotherapies to improve immune and treatment outcomes. <h3>Short conclusion</h3> Given the prevalence of surgery as frontline therapy for solid cancers, the emerging data on postoperative immunosuppression and the rapid development of immunotherapy for oncologic treatment, we believe that future targeted studies of perioperative immunotherapy are warranted.
Evaluating the potential costs and impact of digital health technologies for tuberculosis treatment support
Authors: Ntwali Placide Nsengiyumva, Benjamin Mappin-Kasirer, Olivia Oxlade, Mayara Bastos, Anete Trajman, Dennis Falzon, Kevin Schwartzman
Journal: European Respiratory Journal (2018)

Ensuring adherence and support during treatment of tuberculosis (TB) is a major public health challenge. Digital health technologies could help improve treatment outcomes. We considered their potential cost and impact on treatment for active or latent TB in Brazil. Decision analysis models simulated two adult cohorts with 1) drug-susceptible active TB, and 2) multidrug-resistant TB, and two cohorts treated with isoniazid for latent TB infection (LTBI): 1) close contacts of persons with active TB, and 2) others newly diagnosed with LTBI. We evaluated four digital support strategies: two different medication monitors, synchronous video-observed therapy (VOT), and two-way short message service (SMS). Comparators were standard directly observed treatment for active TB and self-administered treatment for LTBI. Projected outcomes included costs (2016 US dollars), plus active TB cases and disability-adjusted life years averted among persons with LTBI. For individuals with active TB, medication monitors and VOT are projected to lead to substantial (up to 58%) cost savings, in addition to alleviating inconvenience and cost to patients of supervised treatment visits. For LTBI treatment, SMS and medication monitors are projected to be the most cost-effective interventions. However, all projections are limited by the scarcity of published estimates of clinical effect for the digital technologies.