tbuckley/cabot-search huggingface dataset:
Lethal autonomous weapons
Authors: Emilia Javorsky, Max Tegmark, Ira Helfand
Journal: BMJ (2019)

Advances in artificial intelligence are creating the potential to develop fully autonomous lethal weapons. 1 These weapons would remove all human control over the use of deadly force.The medical community has a long history of advocacy against the development of lethal weapons, and the World and American Medical Associations both advocate total bans on nuclear, chemical, and biological weapons. 2 But while some nations and non-governmental organisations have called for a legally binding ban on these new weapons, 3 4 the medical community has been conspicuously absent from this discourse.
FLT3 and NPM1 Are Powerful Determinants of Outcome in Acute Myeloid Leukemia Patients Treated with Autologous Stem Cell Transplantation: An Analysis By the Acute Leukemia Working Party of the EBMT
Authors: Roni Shouval, Myriam Labopin, David Bomze, Gabriela M Baerlocher, Robin Foà, Didier Blaise, Mathias Haenel, Edouard Forcade, Anne Huynh, Riccardo Saccardi, Giuseppe Milone, Tsila Zuckerman, Péter Reményi, Jordi Esteve, Norbert Claude Gorin, Mohamad Mohty, Arnon Nagler
Journal: Blood (2018)
Topical calcineurin inhibitors in the treatment of oral lichen planus: a systematic review and meta‐analysis
Authors: S.‐L. Sun, J.‐J. Liu, B. Zhong, J.‐K. Wang, X. Jin, H. Xu, F.‐Y. Yin, T.‐N. Liu, Q.‐M. Chen, X. Zeng
Journal: British Journal of Dermatology (2019)

TCS (topical corticosteroids) are the first‐line drug in the treatment of oral lichen planus (OLP). However, the value of topical calcineurin inhibitors (TCI) including tacrolimus, pimecrolimus and ciclosporin for OLP is still controversial. To compare the efficacy and safety of TCI vs. TCS for OLP. The authors searched PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science and four Chinese databases from 1950 to May 2018. The randomized controlled trials comparing TCI and TCS for OLP reported at least one of the following outcomes: improvement of clinical signs and/or symptoms, relapse, blood levels of TCI and adverse events. Twenty‐one trials involving 965 patients were included in the analysis. For the treatment of OLP (3–8 weeks), TCI including tacrolimus, pimecrolimus and ciclosporin were similar to TCS in efficacy. Tacrolimus–TCS resulted in similar outcomes, with relapse at 3 weeks to 6 months. Blood levels of TCI were usually undetectable. In addition, tacrolimus showed a statistically higher incidence of local adverse events than TCS for short‐term treatment. A few systemic adverse events occurred in the tacrolimus and ciclosporin groups, but they were not serious. The evidence for tacrolimus (n = 12), pimecrolimus (n = 3) and ciclosporin (n = 6) demonstrated that treatment with TCI may be an alternative approach when OLP does not respond to the standard protocols. Tacrolimus 0·1% should be the first drug of choice when selecting TCI for short‐term treatment in recalcitrant OLP. Further well‐designed trials are warranted to evaluate the long‐term efficacy and safety of TCI. What's already known about this topic? The main topical drug for oral lichen planus (OLP) is topical corticosteroids (TCS). Patients with OLP who are not responsive to TCS or are at risk of adverse events from TCS need other alternative drugs. Topical calcineurin inhibitors (TCI), including tacrolimus, pimecrolimus and ciclosporin, have become a hot topic in a variety of mucocutaneous immune‐mediated diseases. What does this study add? TCI including tacrolimus, pimecrolimus and ciclosporin were similar to TCS in efficacy for the short‐term treatment of OLP. The local adverse events of tacrolimus were higher than with TCS. A few systemic adverse events were reported with TCI, but they were all tolerable and not serious. The limited evidence for pimecrolimus (three trials) and ciclosporin (six trials) requires further studies to evaluate the short‐term and long‐term efficacy and safety of TCI compared with TCS.
Abstract 11103: Increase of Oxidative Stress Precipitated by Selenium Deficiency Plays a Role in Cardiac Hypofunction in Uremic Cardiomyopathy
Authors: Yuji Hiraoka, Masato Tanabe, Taketoshi Yamazaki, Masatoshi Fujita
Journal: Circulation (2015)

Introduction: Various trace elements are deficient in hemodialysis patients, but the relationship of such deficiencies with cardiac hypofunction is unclear. We examined the deficiencies of trace elements in the blood and hair of hemodialysis patients diagnosed with uremic cardiomyopathy and investigated cardiac hypofunction mechanism from myocardial tissue. Methods: Using blood samples, we measured 25 elements including Se, Mn, Cu, and Zn by high-resolution inductively coupled plasma (ICP) mass spectrometry and ICP emission spectral analysis. We also compared glutathione peroxidase (GSHPx) activation and radical formation potential between the uremic cardiomyopathy patient group (n = 22) and a control group with normal cardiac function (n = 30). Using myocardial tissue, we assessed the exacerbation of oxidative stress by 8-hydroxy-2-deoxyguanosine, 4-hydroxy-2-nonenal, and GSHPx staining and microcirculatory disorder by the perivascular fibrosis area ratio (PVFR). We also measured concentrations of elements in hair at the Super Photon ring-8 GeV (SPring-8) facility. Results: Compared with the control group patients, the uremic cardiomyopathy patients had lower selenium (99.7 ± 21.4 vs. 146 ± 23.3 ng/ml, p &lt; 0.00001) and manganese concentrations (0.39 ± 0.15 vs. 0.60 ± 0.12 ng/ml, p &lt; 0.001); they also showed decreased activation of GSHPx (121 ± 33 vs. 328 ± 44 μmol/min/L, p &lt; 0.00001), an antioxidant enzyme involving selenium, with only selenium concentration correlating to left ventricular ejection fraction (p = 0.0009). Oxidative stress marker staining, radical formation potential in serum, and PVFR were all augmented in the uremic cardiomyopathic patients (p &lt; 0.001). Conclusions: Selenium concentration decrease in the serum of hemodialysis patients may reflect a decrease in GSHPx activation, increasing oxidative stress, and precipitating a coronary microcirculatory disorder involved in the cardiac hypofunction seen in uremic cardiomyopathy.
Bioinspired nanoplatelets for chemo-photothermal therapy of breast cancer metastasis inhibition
Authors: Hao Ye, Kaiyuan Wang, Menglin Wang, Rongzheng Liu, Hang Song, Na Li, Qi Lu, Wenjuan Zhang, Yuqian Du, Wenqian Yang, Lu Zhong, Yu Wang, Bohong Yu, Hong Wang, Qiming Kan, Haotian Zhang, Yongjun Wang, Zhonggui He, Jin Sun
Journal: Biomaterials (2019)
68Ga-DOTATOC PET/CT Differentiates Meningioma From Dural Metastases
Authors: Marcus Unterrainer, Viktoria Ruf, Harun Ilhan, Franziska Jill Vettermann, Clemens C. Cyran, Maximilian Niyazi, Peter Bartenstein, Joerg-Christian Tonn, Nathalie Lisa Albert
Journal: Clinical Nuclear Medicine (2019)

A 77-year-old woman with history of breast cancer presented with 2 unclear dural contrast-enhancing lesions on MRI; differential diagnoses were breast cancer metastases and meningiomas. On Ga-DOTATOC PET/CT, the temporal lesion showed high uptake and was classified as meningioma, whereas the lesion at the falx showed barely any Ga-DOTATOC uptake uncharacteristic for meningioma and suggestive for a brain metastasis. After resection, histological specimens from the temporal lesion showed meningioma tissue with distinct SSTR2A expression, whereas the falx lesion revealed a breast cancer metastasis without significant SSTR2A expression. Therefore, Ga-DOTATOC PET represents a powerful imaging modality for the evaluation of unclear dural lesions.
Abstract 12315: Which is More Important as a Cause for Exercise Intolerance, Chronotropic Incompetence or Left Ventricular Diastolic Dysfunction?
Authors: Toshihiko Goto, Kazuaki Wakami, Noriyuki Ikehara, Syohei Kikuchi, Takafumi Kato, Hidekatsu Fukuta, Nobuyuki Ohte
Journal: Circulation (2013)

Exercise intolerance is generally considered to be associated with left ventricular (LV) diastolic dysfunction (DD). Chronotropic incompetence (CI) which is common in patients with cardiovascular d...
Genomic analyses of an extensive collection of wild and cultivated accessions provide new insights into peach breeding history
Authors: Yong Li, Ke Cao, Gengrui Zhu, Weichao Fang, Changwen Chen, Xinwei Wang, Pei Zhao, Jian Guo, Tiyu Ding, Liping Guan, Qian Zhang, Wenwu Guo, Zhangjun Fei, Lirong Wang
Journal: Genome biology (2019)

Human selection has a long history of transforming crop genomes. Peach (Prunus persica) has undergone more than 5000 years of domestication that led to remarkable changes in a series of agronomically important traits, but genetic bases underlying these changes and the effects of artificial selection on genomic diversity are not well understood.Here, we report a comprehensive analysis of peach evolution based on genome sequences of 480 wild and cultivated accessions. By focusing on a set of quantitative trait loci (QTLs), we provide evidence supporting that distinct phases of domestication and improvement have led to an increase in fruit size and taste and extended its geographic distribution. Fruit size was predominantly selected during domestication, and selection for large fruits has led to the loss of genetic diversity in several fruit weight QTLs. In contrast, fruit taste-related QTLs were successively selected for by domestication and improvement, with more QTLs selected for during improvement. Genome-wide association studies of 11 agronomic traits suggest a set of candidate genes controlling these traits and potential markers for molecular breeding. Candidate loci for genes that contributed to the adaption to low-chill regions were identified. Furthermore, the genomic bases of divergent selection for fruit texture and local breeding for different flavors between Asian and European/North American cultivars were also determined.Our results elucidate the genetic basis of peach evolution and provide new resources for future genomics-guided peach breeding.
Identification of a Novel Mutation Predisposing to Familial AML and MDS Syndrome By a NGS Approach
Authors: Simona Bernardi, Camilla Zanaglio, Elif Dereli Eke, Federica Cattina, Mirko Farina, Stefania Masneri, Benedetta Rambaldi, Francesca Schieppati, Alessandro Turra, Nicola Polverelli, Enrico Morello, Michele Malagola, Domenico Russo
Journal: Blood (2018)
Berberine Protects Glomerular Podocytes via Inhibiting Drp1-Mediated Mitochondrial Fission and Dysfunction
Authors: Xin Qin, Yan Zhao, Jing Gong, Wenya Huang, Hao Su, Fen Yuan, Ke Fang, Dingkun Wang, Jingbin Li, Xin Zou, Lijun Xu, Hui Dong, Fuer Lu
Journal: Theranostics (2019)

Elevated levels of plasma free fatty acid (FFA) and disturbed mitochondrial dynamics play crucial roles in the pathogenesis of diabetic kidney disease (DKD).However, the mechanisms by which FFA leads to mitochondrial damage in glomerular podocytes of DKD and the effects of Berberine (BBR) on podocytes are not fully understood.Methods: Using the db/db diabetic mice model and cultured mouse podocytes, we investigated the molecular mechanism of FFA-induced disturbance of mitochondrial dynamics in podocytes and testified the effects of BBR on regulating mitochondrial dysfunction, podocyte apoptosis and glomerulopathy in the progression of DKD.Results: Intragastric administration of BBR for 8 weeks in db/db mice significantly reversed glucose and lipid metabolism disorders, podocyte damage, basement membrane thickening, mesangial expansion and glomerulosclerosis.BBR strongly inhibited podocyte apoptosis, increased reactive oxygen species (ROS) generation, mitochondrial fragmentation and dysfunction both in vivo and in vitro.Mechanistically, BBR could stabilize mitochondrial morphology in podocytes via abolishing palmitic acid (PA)-induced activation of dynamin-related protein 1 (Drp1).Conclusions: Our study demonstrated for the first time that BBR may have a previously unrecognized role in protecting glomerulus and podocytes via positively regulating Drp1-mediated mitochondrial dynamics.It might serve as a novel therapeutic drug for the treatment of DKD.
External validation and recalibration of the Brock model to predict probability of cancer in pulmonary nodules using NLST data
Authors: Audrey Winter, Denise R Aberle, William Hsu
Journal: Thorax (2019)

Introduction We performed an external validation of the Brock model using the National Lung Screening Trial (NLST) data set, following strict guidelines set forth by the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis statement. We report how external validation results can be interpreted and highlight the role of recalibration and model updating. Materials and methods We assessed model discrimination and calibration using the NLST data set. Adhering to the inclusion/exclusion criteria reported by McWilliams et al , we identified 7879 non-calcified nodules discovered at the baseline low-dose CT screen with 2 years of follow-up. We characterised differences between Pan-Canadian Early Detection of Lung Cancer Study and NLST cohorts. We calculated the slope on the prognostic index and the intercept coefficient by fitting the original Brock model to NLST. We also assessed the impact of model recalibration and the addition of new covariates such as body mass index, smoking status, pack-years and asbestos. Results While the area under the curve (AUC) of the model was good, 0.905 (95% CI 0.882 to 0.928), a histogram plot showed that the model poorly differentiated between benign and malignant cases. The calibration plot showed that the model overestimated the probability of cancer. In recalibrating the model, the coefficients for emphysema, spiculation and nodule count were updated. The updated model had an improved calibration and achieved an optimism-corrected AUC of 0.912 (95% CI 0.891 to 0.932). Only pack-year history was found to be significant (p&lt;0.01) among the new covariates evaluated. Conclusion While the Brock model achieved a high AUC when validated on the NLST data set, the model benefited from updating and recalibration. Nevertheless, covariates used in the model appear to be insufficient to adequately discriminate malignant cases.
The IgG2 Isotype of Anti–Transcription Intermediary Factor 1γ Autoantibodies Is a Biomarker of Cancer and Mortality in Adult Dermatomyositis
Authors: Audrey Aussy, Manuel Fréret, Laure Gallay, Didier Bessis, Thierry Vincent, Denis Jullien, Laurent Drouot, Fabienne Jouen, Pascal Joly, Isabelle Marie, Alain Meyer, Jean Sibilia, Brigitte Bader‐Meunier, Eric Hachulla, Mohammed Hamidou, Sophie Huë, Jean‐Luc Charuel, Nicole Fabien, Pierre‐Julien Viailly, Yves Allenbach, Olivier Benveniste, Nadège Cordel, Olivier Boyer
Journal: Arthritis & Rheumatology (2019)

Objective Anti–transcription intermediary factor 1γ (anti‐ TIF 1γ) antibodies are the main predictors of cancer in dermatomyositis ( DM ). Yet, a substantial proportion of anti‐ TIF 1γ–positive DM patients do not develop cancer. This study was undertaken to identify biomarkers to better evaluate the risk of cancer and mortality in DM . Methods This multicenter study was conducted in adult anti‐ TIF 1γ–positive DM patients from August 2013 to August 2017. Anti‐ TIF 1γ autoantibody levels and IgG subclasses were identified using a newly developed quantitative immunoassay. Age, sex, DM signs and activity, malignancy, and creatine kinase ( CK ) level were recorded. Risk factors were determined by univariate and multivariate analysis according to a Cox proportional hazards regression model. Results Among the 51 adult patients enrolled (mean ± SD age 61 ± 17 years; ratio of men to women 0.65), 40 (78%) had cancer and 21 (41%) died, with a mean ± SD survival time of 10 ± 6 months. Detection of anti‐ TIF 1γ IgG2 was significantly associated with mortality ( P = 0.0011) and occurrence of cancer during follow‐up ( P &lt; 0.0001), with a 100% positive predictive value for cancer when the mean fluorescence intensity of anti‐ TIF 1γ IgG2 was &gt;385. None of the patients developed cancer after 24 months of follow‐up. Univariate survival analyses showed that mortality was also associated with age &gt;60 years ( P = 0.0003), active DM ( P = 0.0042), cancer ( P = 0.0031), male sex ( P = 0.011), and CK level &gt;1,084 units/liter ( P = 0.005). Multivariate analysis revealed that age &gt;60 years ( P = 0.015) and the presence of anti‐ TIF 1γ IgG2 ( P = 0.048) were independently associated with mortality. Conclusion Our findings indicate that anti‐ TIF 1γ IgG2 is a potential new biomarker of cancer that should be helpful in identifying the risk of mortality in anti‐ TIF 1γ–positive DM patients.
Abstract 12587: Sodium Current Deficit and Arrhythmogenesis in a Murine Model of Plakophilin-2 Haploinsufficiency
Authors: Marina Cerrone, Maartjie Noorman, Xianming Ling, Halina Chkourko, Feng-Xia Liang, Roel Van Der Nagel, Thomas Hund, Walter Birchmeier, Peter Mohler, Toon A Van Veen, Harold V van Rijen, Mario Delmar
Journal: Circulation (2012)

Mutations in desmosomal protein Plakophilin 2 (PKP2) associate with arrhythmogenic cardiomyopathy (“ARVC”). Cardiac arrhythmias and sudden death can occur in the “concealed” phase of the disease, prior to overt structural damage. The mechanisms underlying these arrhythmias are not understood. Based on previous in vitro data showing cross-talk between PKP2 and the sodium channel (SC) complex, we propose that a decrease in PKP2 causes sodium current (INa) dysfunction, which predisposes the heart to severe arrhythmias if the SC is further challenged. We studied the morphology, histology and ultrastructural features of PKP2-heterozygous-null (PKP2-Hz) murine hearts, and explored the relation between PKP2 abundance, INa and arrhythmias. PKP2-Hz hearts did not show anatomical or histological differences compared to wild-type (WT). Western blot revealed reduced abundance of PKP2, without changes in abundance of other intercalated disc proteins. Tomographic electron microscopy showed loss of desmosomes and expand...
Abstract P236: Analysison Time Course Changes of Adipocytokine Levels and Abdominal Obesity afterQuitting Smoking
Authors: Maki Komiyama, Hiromichi Wada, Hajime Yamakage, Noriko Asahara, Sayaka Shimada, Akira Shimatsu, Tatsuya Morimoto, Yuko Takahashi, Koji Hasegawa
Journal: Circulation (2017)

Background: Adipocytokines are produced and secreted by the adipose tissue and are strongly associated with obesity. Among these cytokines, adiponectin prevents arteriosclerosis. In obesity, the serum adiponectin levels decrease whereas leptin levels increase. However, the association between these two adipocytokines and abdominal obesity after smoking cessation is unknown. Purpose: The present study investigated time-dependent changes after smoking cessation of two adipocytokines, adiponectin and leptin, as well as the changes of body mass index and waist circumstance (WC). Methods: All anti-smoking treatments were conducted according to the Standard Procedures for Anti-Smoking Treatment (originally issued in March 2006 by the Japanese Circulation Society, Japan Lung Cancer Society, and Japanese Cancer Association). The patients were treated with transdermal nicotine patches or the oral administration of varenicline. Among patients who attended our smoking cessation clinic, 56 (37 males and 19 females) successfully quit smoking. We measured their serum leptin and adiponectin levels at baseline, 3 months, and 1 year after beginning smoking cessation. Moreover, the changes in data from before to 3 months and 1 year after smoking cessation were compared by unpaired t-test between patients with a WC increase smaller than the median and those with a WC increase greater than the median. Results: Body mass index and WC significantly increased from baseline to 3 months to 1 year after beginning smoking cessation. The leptin level significantly increased (5.0 ng/ml → 6.2 ng/ml (p &amp;lt; 0.05) → 7.1 ng/ml (p &amp;lt; 0.001)) in proportion to the weight gain. Adiponectin levels, however, did not change after smoking cessation. Using the median ΔWC (+1.8 %) as the cutoff point, patients were divided into two groups. The percent change in adiponectin level from baseline to 1 year was significantly greater in the ΔWC &amp;lt; median group (+13.4 %) than in the ΔWC ≧ median group (-0.6 %) (p = 0.028). Conclusion: Despite weight gain and increased abdominal obesity, serum adiponectin levels did not decrease after smoking cessation. Rather, they increased at 1 year after smoking cessation in patients with less abdominal obesity. Thus, the beneficial effect of smoking cessation may outweigh the adverse effect of weight gain after smoking cessation.
Polymerase Chain Reaction using “V” Shape Thermal Cycling Program
Authors: Rong Chen, Xue Lu, Mei Li, Gangyi Chen, Yun Deng, Feng Du, Juan Dong, Xin Huang, Xin Cui, Zhuo Tang
Journal: Theranostics (2019)

Polymerase chain reaction (PCR) is the most commonly used technique in molecular biology and diagnostics.To achieve faster PCR reaction time, two strategies were employed by previous studies.That includes improving the thermal ramp rate by developing novel devices to reduce the time wasted on temperature transitions and cutting the holding time in every step, which could even lead to compromise in amplification efficiency.Hence the need to further improve the technique.Methods: A different way to achieve fast DNA amplification is developed by using the previously thought wasted time spent on heating and cooling the samples to finish the amplification.That means the holding time of the three procedures are omitted and this could be carried out on the ordinary PCR thermal cyclers.Results: 2/3 of the amplification time is easily saved, compared to the conventionally used method.Additionally, the reaction time could be further reduced by using longer primers with higher melting temperature (Tm).The record time of the "V" shape Polymerase chain reaction (VPCR) conducted on ordinary PCR machine for amplification of a 98 bp fragment is 8 min.Furthermore, VPCR still retains the merits of traditional PCR technique, including specificity, sensitivity, generality, and compatibility with quantitative detection.Conclusion: It is confirmed that the three procedures of PCR could be completed during the dynamic heating and cooling process when the cyclers are run at a moderate thermal ramp rate.As VPCR described here is based on the current PCR system, it could be implemented in any biological Lab immediately and provide great convenience to the people working in the field of life science and human health.
Abstract 13102: Long-term Clinical Effectiveness of Supervised Exercise Therapy versus Endovascular Revascularization for Intermittent Claudication: Results from a Randomized Controlled Trial
Authors: Farzin Fakhry, Ellen V. Rouwet, P. Ted den Hoed, M.G. Myriam Hunink, Sandra Spronk
Journal: Circulation (2012)

Background: Intermittent claudication (IC) is the most common presentation of peripheral arterial disease and is associated with significant functional disability and reduced quality-of-life (QoL)....
Case 10-2019: A 69-Year-Old Man with Progressive Dyspnea
Authors: Katharine E. Black, Sydney B. Montesi, Jennifer F. Feneis, Eugene J. Mark
Journal: New England Journal of Medicine (2019)

A 69-year-old man was evaluated at this hospital because of progressively worsening dyspnea. Results of chest imaging were consistent with fibrotic lung disease, and tests of pulmonary function revealed a restrictive ventilatory deficit with diffusion impairment. A diagnosis was made.
Erlotinib Resistance with EGFR L858R/Y891D Double Mutation in a Patient with Non–Small Cell Lung Cancer
Authors: Jiayue Qin, Juan Wang, Xiaoyi Lin, Jiawei Wang, Zhicheng Xiong, Ruixiao Wang, Hongmei Zhao, Xiangquan Kong
Journal: Journal of Thoracic Oncology (2019)