tbuckley/cabot-search huggingface dataset:
Human female meiosis revised: new insights into the mechanisms of chromosome segregation and aneuploidies from advanced genomics and time-lapse imaging
Authors: Antonio Capalbo, Eva R Hoffmann, Danilo Cimadomo, Filippo Maria Ubaldi, Laura Rienzi
Journal: Human Reproduction Update (2017)

The unbalanced transmission of chromosomes in human gametes and early preimplantation embryos causes aneuploidy, which is a major cause of infertility and pregnancy failure. A baseline of 20% of human oocytes are estimated to be aneuploid and this increases exponentially from 30 to 35 years, reaching on average 80% by 42 years. As a result, reproductive senescence in human females is predominantly determined by the accelerated decline in genetic quality of oocytes from 30 years of age.Understanding mechanisms of chromosome segregation and aneuploidies in the female germline is a crucial step towards the development of new diagnostic approaches and, possibly, for the development of therapeutic targets and molecules. Here, we have reviewed emerging mechanisms that may drive human aneuploidy, in particular the maternal age effect.We conducted a systematic search in PubMed Central of the primary literature from 1990 through 2016 following the PRISMA guidelines, using MeSH terms related to human aneuploidy. For model organism research, we conducted a literature review based on references in human oocytes manuscripts and general reviews related to chromosome segregation in meiosis and mitosis.Advances in genomic and imaging technologies are allowing unprecedented insight into chromosome segregation in human oocytes. This includes the identification of a novel chromosome segregation error, termed reverse segregation, as well as sister kinetochore configurations that were not predicted based on murine models.Elucidation of mechanisms that result in errors in chromosome segregation in meiosis may lead to therapeutic developments that could improve reproductive outcomes by reducing aneuploidy.
Chromatin Accessibility Identifies CTCF As a Gatekeeper of Stemness Functions in Human Hematopoietic Development
Authors: Naoya Takayama, Alex Murison, Shin-ichiro Takayanagi, Sasan Zandi, Nadia Penrod, Amanda Mitchel, James A. Kennedy, Stanley W.K. Ng, Stephanie Zhi-Juan Xie, Mark D. Minden, John E. Dick, Mathieu Lupien
Journal: Blood (2016)
Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography After Concurrent Chemoradiotherapy in Locally Advanced Head-and-Neck Squamous Cell Cancer: The ECLYPS Study
Authors: Tim Van den Wyngaert, Nils Helsen, Laurens Carp, Sara Hakim, Michel J. Martens, Isabel Hutsebaut, Philip R. Debruyne, Annelies L.M. Maes, Joost van Dinther, Carl G. Van Laer, Otto S. Hoekstra, Remco De Bree, Sabine A.E. Meersschout, Olivier Lenssen, Jan B. Vermorken, Danielle Van den Weyngaert, Sigrid Stroobants
Journal: Journal of Clinical Oncology (2017)

Purpose To assess the standardized implementation and reporting of surveillance [18F]fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) scan of the neck in locoregionally advanced head-and-neck squamous cell carcinoma (LAHNSCC) after concurrent chemoradiotherapy (CCRT). Patients and Methods We performed a prospective multicenter study of FDG-PET/CT scanning 12 weeks after CCRT in newly diagnosed patients with LAHNSCC (stage IVa/b) that used standardized reconstruction and Hopkins reporting criteria. The reference standard was histology or > 12 months of clinical follow-up. The primary outcome measure was the negative predictive value (NPV) of FDG-PET/CT scans and other supporting diagnostic test characteristics, including time dependency with increasing follow-up time. Results Of 152 patients, 125 had adequate primary tumor control after CCRT and entered follow-up (median, 20.4 months). Twenty-three (18.4%) had residual neck disease. Overall, NPV was 92.1% (95% CI, 86.9% to 95.3%; null hypothesis: NPV = 85%; P = .012) with sensitivity of 65.2% (95% CI, 44.9% to 81.2%), specificity of 91.2% (95% CI, 84.1% to 95.3%), positive predictive value of 62.5% (95% CI, 45.5% to 76.9%), and accuracy of 86.4% (95% CI, 79.3% to 91.3%). Sensitivity was time dependent and high for residual disease manifesting up to 9 months after imaging but lower (59.7%) for disease detected up to 12 months after imaging. Standardized reporting criteria reduced the number of equivocal reports (95% CI for the difference, 2.6% to 15.0%; P = .003). Test characteristics were not improved with the addition of lymph node CT morphology criteria. Conclusion FDG-PET/CT surveillance using Hopkins criteria 12 weeks after CCRT is reliable in LAHNSCC except for late manifesting residual disease, which may require an additional surveillance scan at 1 year after CCRT to be detected.
Diagnostic accuracy of a clinical diagnosis of idiopathic pulmonary fibrosis: an international case–cohort study
Authors: Simon L.F. Walsh, Toby M. Maher, Martin Kolb, Venerino Poletti, Richard Nusser, Luca Richeldi, Carlo Vancheri, Margaret L. Wilsher, Katerina M. Antoniou, Jüergen Behr, Elisabeth Bendstrup, Kevin Brown, Lucio Calandriello, Tamera J. Corte, Vincent Cottin, Bruno Crestani, Kevin Flaherty, Ian Glaspole, Jan Grutters, Yoshikazu Inoue, Maria Kokosi, Yasuhiro Kondoh, Vasileios Kouranos, Michael Kreuter, Kerri Johannson, Eoin Judge, Brett Ley, George Margaritopoulos, Fernando J. Martinez, Maria Molina-Molina, António Morais, Hilario Nunes, Ganesh Raghu, Christopher J. Ryerson, Moises Selman, Paolo Spagnolo, Hiroyuki Taniguchi, Sara Tomassetti, Dominique Valeyre, Marlies Wijsenbeek, Wim Wuyts, David Hansell, Athol Wells
Journal: European Respiratory Journal (2017)

We conducted an international study of idiopathic pulmonary fibrosis (IPF) diagnosis among a large group of physicians and compared their diagnostic performance to a panel of IPF experts. A total of 1141 respiratory physicians and 34 IPF experts participated. Participants evaluated 60 cases of interstitial lung disease (ILD) without interdisciplinary consultation. Diagnostic agreement was measured using the weighted kappa coefficient (κ w ). Prognostic discrimination between IPF and other ILDs was used to validate diagnostic accuracy for first-choice diagnoses of IPF and were compared using the C-index. A total of 404 physicians completed the study. Agreement for IPF diagnosis was higher among expert physicians (κ w =0.65, IQR 0.53–0.72, p&lt;0.0001) than academic physicians (κ w =0.56, IQR 0.45–0.65, p&lt;0.0001) or physicians with access to multidisciplinary team (MDT) meetings (κ w =0.54, IQR 0.45–0.64, p&lt;0.0001). The prognostic accuracy of academic physicians with &gt;20 years of experience (C-index=0.72, IQR 0.0–0.73, p=0.229) and non-university hospital physicians with more than 20 years of experience, attending weekly MDT meetings (C-index=0.72, IQR 0.70–0.72, p=0.052), did not differ significantly (p=0.229 and p=0.052 respectively) from the expert panel (C-index=0.74 IQR 0.72–0.75). Experienced respiratory physicians at university-based institutions diagnose IPF with similar prognostic accuracy to IPF experts. Regular MDT meeting attendance improves the prognostic accuracy of experienced non-university practitioners to levels achieved by IPF experts.
Pulmonary Function and Sleep Breathing: Two New Targets for Type 2 Diabetes Care
Authors: Albert Lecube, Rafael Simó, Maria Pallayova, Naresh M Punjabi, Carolina López-Cano, Cecilia Turino, Cristina Hernández, Ferran Barbé
Journal: Endocrine Reviews (2017)

Population-based studies showing the negative impact of type 2 diabetes (T2D) on lung function are overviewed. Among the well-recognized pathophysiological mechanisms, the metabolic pathways related to insulin resistance (IR), low-grade chronic inflammation, leptin resistance, microvascular damage, and autonomic neuropathy are emphasized. Histopathological changes are exposed, and findings reported from experimental models are clearly differentiated from those described in humans. The accelerated decline in pulmonary function that appears in patients with cystic fibrosis (CF) with related abnormalities of glucose tolerance and diabetes is considered as an example to further investigate the relationship between T2D and the lung. Furthermore, a possible causal link between antihyperglycemic therapies and pulmonary function is examined. T2D similarly affects breathing during sleep, becoming an independent risk factor for higher rates of sleep apnea, leading to nocturnal hypoxemia and daytime sleepiness. Therefore, the impact of T2D on sleep breathing and its influence on sleep architecture is analyzed. Finally, the effect of improving some pathophysiological mechanisms, primarily IR and inflammation, as well as the optimization of blood glucose control on sleep breathing is evaluated. In summary, the lung should be considered by those providing care for people with diabetes and raise the central issue of whether the normalization of glucose levels can improve pulmonary function and ameliorate sleep-disordered breathing. Therefore, patients with T2D should be considered a vulnerable group for pulmonary dysfunction. However, further research aimed at elucidating how to screen for the lung impairment in the population with diabetes in a cost-effective manner is needed.
Omega-3 (ω3) supplementation versus omega-6 (ω6) supplementation for fatigue among breast cancer survivors: A URCC NCORP RCT.
Authors: Luke Joseph Peppone, Karen Michelle Mustian, Gilbert D. A. Padula, Charles Stewart Kamen, Joseph John Guido, Matthew Asare, Ian Kleckner, Anita Roselyn Peoples, Kenneth Usuki, Jeremy Michael Deutsch, Sharon Cole, Michelle Christine Janelsins
Journal: Journal of Clinical Oncology (2016)

10128 Background: Cancer-related fatigue (CRF) is one of the most troublesome side effects for survivors and is associated with increased inflammation levels. We conducted a multi-site, blinded phase II RCT examining the efficacy of supplementation rich in ω3 fats (fish oil), which has anti-inflammatory properties, versus supplementation rich in ω6 fats (soybean oil) for improving CRF through the URCC NCORP. Methods: Breast cancer survivors between 4-36 months post-adjuvant therapy with a CRF level of 4 or greater (0-10 scale) were stratified by baseline CRF (4-6 = moderate and 7-10 = high) and randomized into 3 arms: 1) High-dose ω3 (ω3; 6 g/day), 2) Low-dose ω3/Low-dose ω6 (ω3/ω6; ω3: 3 g/day and ω6: 3 g/day) and 3) High-dose ω6 (ω6; 6 g/day) for 6 weeks. CRF was assessed via the Symptom Inventory (SI) and Brief Fatigue Inventory (BFI) at pre- and post-intervention. Results: 108 female breast cancer survivors were accrued (93% white, mean age = 60). Mean baseline CRF levels did not differ between groups (ω3 = 6.5, ω3/ω6 = 6.2, ω6 = 6.5; p = 0.75). Biochemical blood analyses confirmed high compliance in all arms with minimal contamination. ANCOVAs, controlling for baseline CRF, revealed significant differences between groups on the SI (SI Change score: ω6 = -2.5 vs. ω3/ω6 = -2.1 vs. ω3 = -0.9; p = 0.02; Cohen’s d= 0.73). Results were similar for BFI scores, although the differences did not reach statistical significance (BFI Change score: ω6 = -2.2 vs. ω3/ω6 = -1.5 vs. ω3 = -1.5; p = 0.24). Stratified analyses showed survivors with high baseline CRF significantly improved on ω6 fats compared to ω3 fats (BFI Change score: ω6 = -3.0 vs. ω3 = -1.7; p = 0.04; Cohen’s d= 0.79) while patients with moderate baseline CRF improved equally with no between-group difference (BFI Change score: ω6 = -1.3 vs. ω3 = -1.3; p = 0.98). Conclusions: High-dose ω6 supplementation from soybean oil significantly reduced CRF compared to high-dose ω3 supplementation in breast cancer survivors, particularly those with high baseline CRF as shown across multiple fatigue measures. Further analyses are underway to determine the mechanism of action of ω6 fats for CRF. Funding: NCI R03CA175599 & UG1CA189961. Nordic Naturals, Inc. supplied all study agents. Clinical trial information: NCT02352779.
Editorial: Clinical Trials in Raynaud's Phenomenon: A Spoonful of Sugar (Pill) Makes the Medicine Go Down (in Flames)
Authors: James R. Seibold, Fredrick M. Wigley
Journal: Arthritis & Rheumatology (2017)

The peripheral vascular disease in systemic sclerosis (scleroderma) is a challenging problem because it presents with both vasospasm and an underlying structural vascular disease that leads not only to severe Raynaud phenomenon but often critical digital ischemia with progressive tissue damage or acute ulceration. While current therapy with a calcium channel blocker alone or combined with another vasodilating agent provides some modest benefit, it does not provide adequate control of Raynaud's events in many patients with scleroderma. Vasodilating therapy alone also does not address the underlying biological process causing progressive vascular disease.

This article is protected by copyright. All rights reserved.
<i>In Vitro</i> Evaluation of Mitochondrial Function and Estrogen Signaling in Cell Lines Exposed to the Antiseptic Cetylpyridinium Chloride
Authors: Sandipan Datta, Guochun He, Alexey Tomilov, Sunil Sahdeo, Michael S. Denison, Gino Cortopassi
Journal: Environmental Health Perspectives (2017)

Background: Quaternary ammonium salts (QUATS), such as cetylpyridinium chloride (CPC) and benzalkonium chloride (BAK), are frequently used in antiseptic formulations, including toothpastes, mouthwashes, lozenges, throat and nasal sprays, and as biocides. Although in a recent ruling, the U.S. Food and Drug Administration (FDA) banned CPC from certain products and requested more data on BAK's efficacy and safety profile, QUATS, in general, and CPC and BAK, in particular, continue to be used in personal health care, food, and pharmaceutical and cleaning industries. Objectives: We aimed to assess CPC's effects on mitochondrial toxicity and endocrine disruption in vitro. Method: Mitochondrial O2 consumption and adenosine triphosphate (ATP) synthesis rates of osteosarcoma cybrid cells were measured before and after CPC and BAK treatment. Antiestrogenic effects of the compounds were measured by a luciferase-based assay using recombinant human breast carcinoma cells (VM7Luc4E2, ERalpha-positive). Results: CPC inhibited both mitochondrial O2 consumption [half maximal inhibitory concentration (IC50): 3.8μM] and ATP synthesis (IC50: 0.9μM), and additional findings supported inhibition of mitochondrial complex 1 as the underlying mechanism for these effects. In addition, CPC showed concentration-dependent antiestrogenic activity half maximal effective concentration [(EC50): 4.5μM)]. BAK, another antimicrobial QUATS that is structurally similar to CPC, and the pesticide rotenone, a known complex 1 inhibitor, also showed mitochondrial inhibitory and antiestrogenic effects. In all three cases, there was overlap of the antiestrogenic activity with the mitochondrial inhibitory activity. Conclusions: Mitochondrial inhibition in vitro occurred at a CPC concentration that may be relevant to human exposures. The antiestrogenic activity of CPC, BAK, rotenone, and triclosan may be related to their mitochondrial inhibitory activity. Our findings support the need for additional research on the mitochondrial inhibitory and antiestrogenic effects of QUATS, including CPC and BAK. https://doi.org/10.1289/EHP1404
Uniform Nomenclature to Describe Clinical Features of Pigmented Lesions
Authors: Kelsey S. Flood, Gary J. Martin, June K. Robinson
Journal: JAMA Dermatology (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Dermatology journal
Somatic Mutations Are Frequently Detected in Chronic Myeloid Leukemia in Chronic Phase and Do Not Affect Response to Tyrosine-Kinase Inhibitors
Authors: Chiara Elena, Anna Gallì, Antonio Bianchessi, Virginia Valeria Ferretti, Silvia Zibellini, Silvia Catricalà, Celeste Calvello, Barbara Rocca, Paolo Bernasconi, Ettore Rizzo, Elisabetta Molteni, Luca Malcovati, Matteo Giovanni Della Porta, Ester Maria Orlandi, Mario Cazzola
Journal: Blood (2016)
Therapies for advanced stage hepatocellular carcinoma with macrovascular invasion or metastatic disease: A systematic review and meta‐analysis
Authors: Richard S. Finn, Andrew X. Zhu, Wigdan Farah, Jehad Almasri, Feras Zaiem, Larry J. Prokop, Mohammad Hassan Murad, Khaled Mohammed
Journal: Hepatology (2017)

Hepatocellular carcinoma (HCC) is a complex disease most commonly arising in the background of chronic liver disease. In the past two decades, there has been a significant increase in our understanding of both the clinical and molecular heterogeneity of HCC. There has been a robust increase in clinical trial activity in patients with poor prognostic factors, such as macrovascular invasion and extrahepatic spread (EHS). We aimed to synthesize the evidence for the treatment of patients with advanced HCC based on these baseline characteristics, including patients with both Child-Pugh (CP) scores of A and B. A comprehensive search of several databases from each database inception to February 15, 2016 any language was conducted. We included 14 studies (three randomized controlled studies [RCTs] and 11 observational studies). We included studies that compared sorafenib, transarterial bland embolization/transarterial chemoembolization, yttrium-90/radiation therapy, ablation (or combination), and no therapy. Two RCTs comparing sorafenib to best supportive care demonstrated a consistent improvement in overall survival (OS) for patients with advanced HCC and metastatic vascular invasion (MVI) and/or EHS and CP A liver disease (hazard ratio, 0.66 [95% confidence interval, 0.51-0.87]; I2 = 0%). Several observational studies evaluated locoregional therapies alone or in combination with other treatments and were limited by very-low-quality of evidence. This was true for both patients with EHS and MVI.In patients with advanced HCC and CP A liver function, sorafenib is the only treatment that has been shown to improve OS in randomized studies. High-quality data supporting the use of other treatment modalities in this setting, or in the setting of patients with less compensated (CP B) liver disease, are lacking. (Hepatology 2018;67:422-435).
Abstract 19652: Gender Disparities Among Patients Undergoing Transcatheter Aortic Valve Replacement
Authors: Michael A Gaglia, Rebecca M Torguson, Michael J Lipinski, Itsik Ben-Dor, Lowell Satler, Augusto Pichard, Ron Waksman
Journal: Circulation (2015)

Background: Previous studies have suggested higher rates of mortality among female patients undergoing surgical aortic valve replacement, but gender disparities in transcatheter aortic valve replacement (TAVR) patients are not well-studied. Objectives: We sought to compare 30-day and 1-year outcomes in female vs. male patients undergoing TAVR for severe, symptomatic AS. Methods: Consecutive patients undergoing TAVR at a single center were stratified according to gender. We compared female v. male patients in regards to the incidence of comorbidities, in addition to 30-day and 1-year outcomes according to the Valve Academic Research Consortium (VARC) criteria. A Cox proportional hazards regression was performed to assess for an independent association of female gender and mortality at 1 year. Results: The study population included 362 female and 354 male patients. Females were less likely to suffer from a number of comorbidities than males, including a coronary artery disease (63.8% v. 84.3%, p&lt;0.001), peripheral vascular disease (26.3% v. 41.8%, p&lt;0.001), and chronic renal insufficiency (41.7% v. 53.6%, p=0.002). Despite this, females had a higher average STS score (9.9 v. 8.2; p&lt;0.001). Females were more likely to have a life-threatening bleed (9.9% vs. 5.4%, p=0.03), although there was only a trend for more major vascular complications (11.8% vs. 8.2%, p=0.11). Females also had higher rates of in-hospital (7.8% vs. 3.7%, p=0.02) and 30-day mortality (9.7% vs. 5.6%, p=0.04), although there was no difference at 1 year (21.0% vs. 21.5%, p=0.88). Following multivariable adjustment, there was no independent association of gender and mortality at 1 year. Conclusions: Females undergoing TAVR suffer higher rates of short-term mortality, but outcomes at 1 year are similar to males. This suggests that there may be a hazard to female gender periprocedurally, but long term this difference is abolished because of a lesser burden of comorbidities.
Selecting patients for resection after primary chemotherapy for non-metastatic pancreatic adenocarcinoma
Authors: M. Reni, S. Zanon, G. Balzano, S. Nobile, C.C. Pircher, M. Chiaravalli, P. Passoni, P.G. Arcidiacono, R. Nicoletti, S. Crippa, N. Slim, C. Doglioni, M. Falconi, L. Gianni
Journal: Annals of Oncology (2017)
Risk of dying is higher in patients admitted to intensive care at weekends, finds Austrian study
Authors: Susan Mayor
Journal: BMJ (2017)

Patients admitted to intensive care units (ICUs) at weekends are at higher risk of death than those admitted on a weekday, even after adjusting for severity of illness, an Austrian registry study has found.1 But patients already on ICUs had lower mortality at weekends than weekdays.

“This effect requires thoughtful considerations both by clinicians and policy makers, because in the 21st century the day of admission should not influence patient outcomes,” said Paul Zajic from the Medical University Graz, Austria, who was lead author of the study. 

The study analysed anonymised data for all 167 425 adult patients admitted to 119 ICUs in Austria between 2012 …
脂質ベースナノ粒子類似原始細胞による癌細胞へのin situ PCR増幅Sleeping Beautyトランスポゾン遺伝子の標的デリバリー【Powered by NICT】
Authors: Ma Kun, Fu Duo, Yu Dongli, Cui Changhao, Wang Li, Guo Zhaoming, Mao Chuanbin
Journal: Biomaterials (2017)
Systolic blood pressure reduction during the first 24 h in acute heart failure admission: friend or foe?
Authors: Gad Cotter, Marco Metra, Beth A. Davison, Guillaume Jondeau, John G.F. Cleland, Robert C. Bourge, Olga Milo, Christopher M. O'Connor, John D. Parker, Guillermo Torre‐Amione, Dirk J. van Veldhuisen, Isaac Kobrin, Maurizio Rainisio, Stefanie Senger, Christopher Edwards, John J.V. McMurray, John R. Teerlink
Journal: European Journal of Heart Failure (2017)
Aspergillus fumigatus alkaline protease 1 (Alp1/Asp f13) in the airways correlates with asthma severity
Authors: Trisha Basu, Seyedmojtaba Seyedmousavi, Janyce A. Sugui, Nariman Balenga, Ming Zhao, Kyung Joo Kwon Chung, Sabrina Biardel, Michel Laviolette, Kirk M. Druey
Journal: Journal of Allergy and Clinical Immunology (2017)