tbuckley/cabot-search huggingface dataset:
Prevalence of Intracranial Aneurysm in Women With Fibromuscular Dysplasia
Authors: Henry D. Lather, Heather L. Gornik, Jeffrey W. Olin, Xiaokui Gu, Steven T. Heidt, Esther S. H. Kim, Daniella Kadian-Dodov, Aditya Sharma, Bruce Gray, Michael R. Jaff, Yung-Wei Chi, Pamela Mace, Eva Kline-Rogers, James B. Froehlich
Journal: JAMA Neurology (2017)

<h3>Importance</h3> The prevalence of intracranial aneurysm in patients with fibromuscular dysplasia (FMD) is uncertain. <h3>Objective</h3> To examine the prevalence of intracranial aneurysm in women diagnosed with FMD. <h3>Design, Setting, and Participants</h3> This cross-sectional study included 669 women with intracranial imaging registered in the US Registry for Fibromuscular Dysplasia, an observational disease-based registry of patients with FMD confirmed by vascular imaging and currently enrolling at 14 participating US academic centers. Registry enrollment began in 2008, and data were abstracted in September 2015. Patients younger than 18 years at the time of FMD diagnosis were excluded. Imaging reports of all patients with reported internal carotid, vertebral, or suspected intracranial artery aneurysms were reviewed. Only saccular or broad-based aneurysms 2 mm or larger in greatest dimension were included. Extradural aneurysms in the internal carotid artery were included; fusiform aneurysms, infundibulae, and vascular segments with uncertainty were excluded. <h3>Main Outcomes and Measures</h3> Percentage of women with FMD with intracranial imaging who had an intracranial aneurysm. <h3>Results</h3> Of 1112 female patients in the registry, 669 (60.2%) had undergone intracranial imaging at the time of enrollment (mean [SD] age at enrollment, 55.6 [10.9] years). Of the 669 patients included in the analysis, 86 (12.9%; 95% CI, 10.3%-15.9%) had at least 1 intracranial aneurysm. Of these 86 patients, 25 (53.8%) had more than 1 intracranial aneurysm. Intracranial aneurysms 5 mm or larger occurred in 32 of 74 patients (43.2%), and 24 of 128 intracranial aneurysms (18.8%) were in the posterior communicating or posterior arteries. The presence of intracranial aneurysm did not vary with location of extracranial FMD involvement. A history of smoking was significantly associated with intracranial aneurysm: 42 of 78 patients with intracranial aneurysm (53.8%) had a smoking history vs 163 of 564 patients without intracranial aneurysm (28.9%;<i>P</i> &lt; .001). <h3>Conclusions and Relevance</h3> The prevalence of intracranial aneurysm in women diagnosed with FMD is significantly higher than reported in the general population. Although the clinical benefit of screening for intracranial aneurysm in patients with FMD has yet to be proven, these data lend support to the recommendation that all patients with FMD undergo intracranial imaging if not already performed.
Physicians Rarely Elicit Critically Ill Patients’ Previously Expressed Treatment Preferences in Intensive Care Units
Authors: Jared Chiarchiaro, Natalie C. Ernecoff, Leslie P. Scheunemann, Catherine L. Hough, Shannon S. Carson, Michael W. Peterson, Wendy G. Anderson, Jay S. Steingrub, Robert M. Arnold, Douglas B. White
Journal: American Journal of Respiratory and Critical Care Medicine (2017)
Dementia is now leading cause of death in women in England
Authors: Adrian O’Dowd
Journal: BMJ (2017)

Dementia has become the leading cause of death among women in England, overtaking heart disease, and the second most common cause among men, show new figures from Public Health England.

The agency published its Health Profile for England on 13 July,1 which it said was the first time it had used its full population health data to give an overall picture of the health of England.

Overall, people in England are living longer than ever, said the report, with life expectancy now reaching 79.5 years for men and 83.1 years for women, but much of the extra time is spent in poor health.

Lower back and neck pain are the biggest …
Erratum: GBD 2010 Country Collaboration. GBD 2010 country results: A global public good (The Lancet (2013) 381 (965-970))
Authors: A. Halasa, Lorenzo Monasta, Marcella Montico, Kovin S. Naidoo, Luca Ronfani, Joshua A. Salomon, Kenji Shibuya, Giorgio Tamburlini
Journal: The Lancet (2013)
A type 2 cytokine axis for thymus emigration
Authors: Andrea J. White, Song Baik, Sonia M. Parnell, Amanda M. Holland, Frank Brombacher, William E. Jenkinson, Graham Anderson
Journal: The Journal of Experimental Medicine (2017)

In the thymus, stromal microenvironments support a developmental program that generates mature T cells ready for thymic exit. The cellular and molecular specialization within thymic stromal cells that enables their regulation of specific stages of thymocyte development is poorly understood. Here, we show the thymic microenvironment expresses the type 2 IL-4R complex and is functionally responsive to its known ligands, IL-4 and IL-13. Absence of IL-4Rα limits thymocyte emigration, leading to an intrathymic accumulation of mature thymocytes within medullary perivascular spaces and reduced numbers of recent thymic emigrants. Thymus transplantation shows this requirement maps to IL-4Rα expression by stromal cells, and we provide evidence that it regulates thymic exit via a process distinct from S1P-mediated migration. Finally, we reveal a cellular mechanism by which IL-4+IL-13+ invariant NKT cells are necessary for IL-4Rα signaling that regulates thymic exit. Collectively, we define a new axis for thymic emigration involving stimulation of the thymic microenvironment via type 2 cytokines from innate T cells.
Hemoglobin A<sub>1c</sub> as a Surrogate for Clinical Outcomes in Diabetes Studies—Reply
Authors: Kasia J. Lipska, Harlan M. Krumholz
Journal: JAMA (2017)

In Reply We agree with Dr Venker that HbA1c levels were not the same in the placebo and active treatment groups of the EMPA-REG OUTCOME and LEADER trials and appreciate his careful analysis of HbA1c levels over time. However, we still characterize these differences in HbA1c levels as “small.”
Analysis of ASXL1, IDH1, IDH2, c-CBL, and WT1 Mutations in De Novo Acute Myeloid Leukaemia
Authors: Mariam Ibañez, Esperanza Such, Jose Cervera, Irene Luna, Sandra Dolz, Inés Gómez-Seguí, Maria López-Pavia, Beatriz Costan, Eva Barragan, Oscar Fuster, Marta Llop, Silvestre Oltra, Federico Moscardo, Pau Montesinos, David Martinez-Cuadrón, Miguel A. Sanz
Journal: Blood (2011)
Hair Repigmentation During Immunotherapy Treatment With an Anti–Programmed Cell Death 1 and Anti–Programmed Cell Death Ligand 1 Agent for Lung Cancer
Authors: Noelia Rivera, Aram Boada, M. Isabel Bielsa, M. Teresa Fernández-Figueras, Enric Carcereny, M Teresa Moran, Carlos Ferrándiz
Journal: JAMA Dermatology (2017)

New targeted therapies for cancer have been released in recent years, opening new horizons in the treatment of patients with cancer. However, their related adverse events (AE) are not fully characterized. Hair repigmentation (HR) is a nondescribed effect secondary to anti-programmed cell death 1 (anti-PD-1) and anti-programmed cell death ligand 1 (anti-PD-L1 ) therapy for treatment of lung cancer (LC), in opposition to the vitiligo reactions that develop during melanoma treatment.To describe a new adverse event occurring during anti-PD-1/anti-PD-L1 therapy for LC.A case series from a descriptive observation of 14 patients with HR after anti-PD-1/anti-PD-L1 treatment, recruited between September and December, 2016, who were followed up to detect whether they developed cutaneous AE at the time HR was detected. The patients had all been treated in the dermatology department at Hospital Universitari Germans Trias i Pujol, Badalona, Spain.Clinical observation of HR during anti-PD-1/anti-PD-L1 therapy for LC, proved by comparing old pictures provided by the patients and recent pictures taken during the follow-up.Fourteen patients (13 men and 1 woman; mean age, 64.9 years) receiving anti-PD-1 or anti-PD-L1 therapy for non-small-cell lung cancer (NSCLC) presented hair repigmentation during follow-up. This hair repigmentation consisted in a diffuse darkening of the hair in 13 of 14 patients, or in black patches between white hairs in 1. Thirteen of 14 patients presented a good clinical response to the treatment, with at least stable disease, and only 1 had to stop the therapy after only 4 cycles of treatment owing to a life-threatening progression of the disease.We present to our knowledge the first report of hair repigmentation owing to anti-PD-1/anti-PD-L1 therapy for lung cancer in a series of 14 patients. Hair repigmentation may be a good response marker in patients receiving anti-PD1/anti-PD-L1 therapy for LC.
DNA methylation–based immune response signature improves patient diagnosis in multiple cancers
Authors: Jana Jeschke, Martin Bizet, Christine Desmedt, Emilie Calonne, Sarah Dedeurwaerder, Soizic Garaud, Alexander Koch, Denis Larsimont, Roberto Salgado, Gert Van den Eynden, Karen Willard Gallo, Gianluca Bontempi, Matthieu Defrance, Christos Sotiriou, François Fuks
Journal: Journal of Clinical Investigation (2017)

The tumor immune response is increasingly associated with better clinical outcomes in breast and other cancers. However, the evaluation of tumor-infiltrating lymphocytes (TILs) relies on histopathological measurements with limited accuracy and reproducibility. Here, we profiled DNA methylation markers to identify a methylation of TIL (MeTIL) signature that recapitulates TIL evaluations and their prognostic value for long-term outcomes in breast cancer (BC).MeTIL signature scores were correlated with clinical endpoints reflecting overall or disease-free survival and a pathologic complete response to preoperative anthracycline therapy in 3 BC cohorts from the Jules Bordet Institute in Brussels and in other cancer types from The Cancer Genome Atlas.The MeTIL signature measured TIL distributions in a sensitive manner and predicted survival and response to chemotherapy in BC better than did histopathological assessment of TILs or gene expression-based immune markers, respectively. The MeTIL signature also improved the prediction of survival in other malignancies, including melanoma and lung cancer. Furthermore, the MeTIL signature predicted differences in survival for malignancies in which TILs were not known to have a prognostic value. Finally, we showed that MeTIL markers can be determined by bisulfite pyrosequencing of small amounts of DNA from formalin-fixed, paraffin-embedded tumor tissue, supporting clinical applications for this methodology.This study highlights the power of DNA methylation to evaluate tumor immune responses and the potential of this approach to improve the diagnosis and treatment of breast and other cancers.This work was funded by the Fonds National de la Recherche Scientifique (FNRS) and Télévie, the INNOVIRIS Brussels Region BRUBREAST Project, the IUAP P7/03 program, the Belgian "Foundation against Cancer," the Breast Cancer Research Foundation (BCRF), and the Fonds Gaston Ithier.
Abstract 258: Human 450delACryAB Overexpression Associated with Protein Aggregation Uncovers a Novel Mechanism for Inheritable Myofibrillar-Sparing Cardiomyopathy in Mice
Authors: Huali Zhang, Qiang Liu, Pattraranee Limphong, Adam R Wende, Xiaohui Wang, Xiuquan Zhang, Gregory W Pratt, Elisabeth Christians, Ivor J Benjamin
Journal: Circulation Research (2012)

Desmin-related cardiomyopathy (DRC) belongs to the family of myofibrillar diseases characterized by the presence of toxic desmin-positive aggregates and degeneration at Z-disk structures. DRC has been linked to the mutations in the desmin, αBcrystallin (CryAB), or myotilin genes. Several human CryAB mutations cause multisystem disorders and experimental models of R120GCryAB in transgenic mice strikingly recapitulate similar phenotype observed in patients. In this context, we have generated the 450delACryAB linked to inheritable cataracts in neonatal rat cardiomyocytes and mice hearts. 450delACryAB formed aggregates or aggresomes, and recruited HSP25 into the insoluble fraction in the cardiomyocytes. However, heart-specific 450delA CryAB overexpression neither causes desmin-related cardiomyopathy nor exacerbates pressure overload-induced hypertrophy. To our knowledge, this is the first report of compensation to protein aggregates formation abrogates the development of cardiomyopathy and suggests possible insights into disease-specific susceptibility and resistance. We found that there are several different characteristics between 450delACryAB and R120GCryAB. First, 450delACryAB formed much less soluble oligomers than R120GCryAB in cardiomyocytes, and translocated almost into the insoluble fraction when overexpressing in the hearts. Secondly, 450delACryAB aggregates displayed small pattern without either disturbance of desmin striated network or sequestration of desmin into the insoluble fraction, although 450delACryAB interacts with desmin in the heart. Thirdly, doxycycline treatment did not suppress 450delACryAB aggregates. Nonetheless, 450delACryAB aggregates caused the accumulation of ubiquitinated proteins and subsequently upregulated autophagy activity in mice heart, which is similar to R120GCryAB aggregates. The interaction of 450delACryAB with AKT, p62 and Beclin 1 might contribute to impaired UPS dysfunction and activation of autophagy. The findings reported here suggest that such differences contribute to the variable penetrance and pathogenesis in humans.
Behavioral Counseling Interventions to Promote a Healthy Diet and Physical Activity for Cardiovascular Disease Prevention in Adults With Cardiovascular Risk Factors
Authors: Alex H. Krist, Karina W. Davidson, Carol M. Mangione, Michael J. Barry, Michael Cabana, Aaron B. Caughey, Katrina Donahue, Chyke A. Doubeni, John W. Epling, Martha Kubik, Seth Landefeld, Gbenga Ogedegbe, Lori Pbert, Michael Silverstein, Melissa A. Simon, Chien-Wen Tseng, John B. Wong
Journal: JAMA (2020)

Cardiovascular disease (CVD) is a leading cause of death in the US. Known modifiable risk factors for CVD include smoking, overweight and obesity, diabetes, elevated blood pressure or hypertension, dyslipidemia, lack of physical activity, and unhealthy diet. Adults who adhere to national guidelines for a healthy diet and physical activity have lower cardiovascular morbidity and mortality than those who do not. All persons, regardless of their CVD risk status, benefit from healthy eating behaviors and appropriate physical activity.To update its 2014 recommendation, the USPSTF commissioned a review of the evidence on behavioral counseling to promote a healthy diet and physical activity for CVD prevention in adults with cardiovascular risk factors.This recommendation statement applies to adults 18 years or older with known hypertension or elevated blood pressure, those with dyslipidemia, or those who have mixed or multiple risk factors such as metabolic syndrome or an estimated 10-year CVD risk of 7.5% or greater. Adults with other known modifiable cardiovascular risk factors such as abnormal blood glucose levels, obesity, and smoking are not included in this recommendation.The USPSTF concludes with moderate certainty that behavioral counseling interventions have a moderate net benefit on CVD risk in adults at increased risk for CVD.The USPSTF recommends offering or referring adults with CVD risk factors to behavioral counseling interventions to promote a healthy diet and physical activity. (B recommendation).
Phase I study of nab-paclitaxel, gemcitabine, and bevacizumab in advanced cancers.
Authors: Shiraj Sen, Sarina Anne Piha-Paul, Shumei Kato, Daniel D. Karp, Filip Janku, Siqing Fu, Aung Naing, Shubham Pant, Apostolia Maria Tsimberidou, Vivek Subbiah, Razelle Kurzrock, Funda Meric-Bernstam, David S. Hong
Journal: Journal of Clinical Oncology (2017)

2526 Background: Gemcitabine (gem) with nab-paclitaxel (nab-p) is known to have antitumor activity and a favorable toxicity profile. The addition of bevacizumab (bev) to nab-paclitaxel has also been found to enhance nab-paclitaxel cytotoxicity. Methods: We therefore performed a modified 3+3 dose escalation study with 15 dose levels of fixed dose gem 1000 mg/m 2 IV (day 1, 8, 15) and escalating doses of nab-p IV (day 1,8, 15) and bev IV (day 1,15) every 28 days. The study design allowed for the possibility of multiple MTDs. Correlative studies on VEGF polymorphism and response were planned. (NCT01113476). Results: 103 patients (45 male) with advanced cancers were enrolled (19 ovarian, 18 pancreatic, and 18 gastroesophageal (GE) cancers among the most common). All patients were ECOG PS 0-2, median age was 60 years (range 17-85), and 51 patients (50%) were gem refractory with a median of 3 prior lines of therapy. 3 DLTs were observed during dose escalation - one with nab-p 50 mg/m 2 and bev 10 mg/m 2 (grade 3 dysphagia, dehydration), one with nab-p 75 mg/m 2 and bev 10 mg/m 2 (grade 3 cellulitis) and one with nab-p 150 mg/m 2 and bev 5 mg/m 2 (grade 3 bacteremia, hypotension). 2 DLTs were observed among the 13 patients in the nab-p 100 mg/m 2 and bev 5 mg/m 2 expansion cohort (one grade 3 diarrhea, one grade 3 fatigue) and 1 DLT among the 12 patients in the nab-p 75 mg/m 2 and bev 10 mg/m 2 expansion cohort (grade 3 rectal bleed). Dose escalation up to nab-p 125 mg/m 2 and bev 15 mg/m 2 was well tolerated with no MTD. One patient with gem refractory peritoneal papillary carcinoma achieved a complete response, 13 patients (13%) had partial responses (PR), and 54 patients (52%) had prolonged stable disease (pSD) ≥ 12 weeks. 4 patients achieving PR and 26 patients with pSD were previously gem refractory. 3/6 (50%) small cell cancers achieved PR and all 6 of these patients had tumor shrinkage of at least 25%. 4/19 (21%) ovarian cancers achieved PR, 3/18 (17%) GE cancers achieved PR, and 1/18 (6%) pancreatic cancers achieved PR. Conclusions: The combination of gem 1000 mg/m 2 , nab-p 125 mg/m 2 and bev 15 mg/m 2 is safe, well-tolerated, and has activity even at lower doses in advanced malignancies, including gem refractory tumors. Correlative VEGF polymorphism studies are ongoing. Clinical trial information: NCT01113476.
AB0148 Chiropractic management of shoulder capsulitis and knee osteoarthritis
Authors: AP Rozin
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> The treatment of osteoarthritis (OA) of the knees and adhesive capsulitis of the shoulders (SAC) is often disappointing. Recent EULAR clinical guidlines emphasise the role of non-pharmacological treatment modalities for knee OA.<sup>1</sup> Since 1990 some reports confirmed the benefit of chiropractic management for low back pain.<sup>2,3</sup> The theory of the vertebrone laid by Gutzeit (1951) related vertebrogenic nerve involvement with target tissue pathology. Chiropractic method of Kasyan was devised and originally modified for the treatment of spine, shoulders and degenerative disease of the knees.<sup>4,5</sup> <h3>Objectives</h3> To assess the results of modified Kasyan chiropractic treatment for osteoarthritis of the knee and for adhesive capsulitis of the shoulder. <h3>Methods</h3> Twenty nine patients with symptomatic OA of the knees and 37 – with SAC (more than 50% reduction of passive movements on all directions) were referred to chiropractic clinic following failure of long term conventional therapy (physiotherapy, NSAID's, local steroid injections). On admission very high proportion of each group (84% knees and 86% shoulder) were found to have "silent spondylosis": L2–4 or C5-T1 tenderness, paravertebral muscle spasm, and positive X-Ray for spondylosis. None had lumbar or cervical pain. Two-three chiropractic sessions per week (15 ± 11 sessions for knee OA and 10 ± 4 – for SAC) were applied to both the relevant spine and the affected joint (combined therapy). <h3>Results</h3> The results (in percentage of patients) are presented in the Table 1. Once a month maintenance session may be necessary to establish long term results. <h3>Conclusion</h3> When direct therapy to knee or shoulder fails – "silent" spondylosis should be searched. Combined chiropractic therapy is highly effective in both situations. <h3>References</h3> Pendleton A, Arden N, Dougados M, <i>et al</i>. EULAR recommendations for the management of knee osteoarthritis (ESCITIS). Ann Rheum Dis. 2000;59:936–44 Meade TW, Dyer S, Browne W, <i>et al</i>. Randomized comparison of chiropractic and hospital outpatient management for low back pain: results from extended follow up. BMJ 1995;311:349–51 Shekelle PG, Coulter I, Hurwitz EL, <i>et al</i>. Congruence between decisions to initiate chiropractic spinal manipulation for low back pain and appropriateness criteria in North America. Ann Intern Med. 1998;129:9–17 Kasyan N. Manual therapy for spine osteochondrosis. Moskow Medicine, 1985 Rozin A. Chiropractic management of degenerative spine disease. Rheumatic Pain Satellite Symposium, 1999, Freiburg, Germany
Abstract 047: Transgenic troponin T in Zebrafish recapitulates a Unique type of Cardiomyopathy
Authors: Bin He, Xiaojing Sun, Weibin Liu, Xiaolei Xu
Journal: Circulation Research (2013)

Background: Cardiomyopathy-like phenotype has been recently reported in adult zebrafish stressed by either anemia or doxorubicin. However, it still remains unclear whether gene-based manipulation in this emerging animal model can faithfully recapitulate cardiomyopathy phenotypes in mammals. Here, we aim to address this question by generating the first transgenic model for cardiomyopathy in zebrafish. Results: We generated a panel of three transgenic fish lines, including Tg(cmlc2:Tnnt2) that overexpress wild type Tnnt2 in the whole heart, Tg(cmlc2:Tnnt2c) that drive a C-terminal amino acid truncated Tnnt2 (Tnnt2C) in the whole heart, and Tg(vmhc:Tnnt2c) that drives Tnnt2c expression only in the ventricle. Upon overexpression of the Tnnt2C, but not the full-length control, in the heart caused reduced ventricular size but enlarged atrium. A same morphological phenotype was noted in Tg(vmhc:Tnnt2c). At the cellular level, we found significantly reduced size of cardiomyocyte and increased cell proliferation. The morphological remodeling is accompanied by hallmarks of cardiomyopathy including reduced cardiac function and myofibril disarray. Conclusion: Transgenic overexpression of Tnnt2C in zebrafish faithfully recapitulates unique cardiomyopathy phenotypes noted in both human patients harboring the similar mutation and mice transgenic models, underscoring zebrafish as a conserved vertebrate model for cardiomyopathy. Our study further suggested that the dysfunction of Tnnt2C in ventricle is primarily responsible for cardiac phenotypes, while the enlarged atrium is a consequence of a defective ventricle.
Tetherless near-infrared control of brain activity in behaving animals using fully implantable upconversion microdevices
Authors: Ying Wang, Xudong Lin, Xi Chen, Xian Chen, Zhen Xu, Wenchong Zhang, Qinghai Liao, Xin Duan, Xin Wang, Ming Liu, Feng Wang, Jufang He, Peng Shi
Journal: Biomaterials (2017)
Zbtb7a induction in alveolar macrophages is implicated in anti-HLA–mediated lung allograft rejection
Authors: Deepak K. Nayak, Fangyu Zhou, Min Xu, Jing Huang, Moriya Tsuji, Jinsheng Yu, Ramsey Hachem, Andrew E. Gelman, Ross M. Bremner, Michael A. Smith, Thalachallour Mohanakumar
Journal: Science Translational Medicine (2017)

Zbtb7a in alveolar macrophages influences early inflammation and autoimmunity in antibody-mediated rejection of transplanted lungs.
Value of an Immediate Intravesical Instillation of Mitomycin C in Patients with Non–muscle-invasive Bladder Cancer: A Prospective Multicentre Randomised Study in 2243 patients
Authors: Judith Bosschieter, Jakko A. Nieuwenhuijzen, Tessa van Ginkel, André N. Vis, Birgit Witte, Don Newling, Goedele M.A. Beckers, R. Jeroen A. van Moorselaar
Journal: European Urology (2017)