bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II study of α-galactosylceramide-pulsed antigen-presenting cells in patients with advanced or recurrent non-small cell lung cancer
Authors: Toyoda Takahide , Kamata Toshiko , Tanaka Kazuhisa , Ihara Fumie , Takami Mariko , Suzuki Hidemi , Nakajima Takahiro , Ikeuchi Takayuki , Kawasaki Yohei , Hanaoka Hideki , Nakayama Toshinori , Yoshino Ichiro , Motohashi Shinichiro 
Published: March 2020

BackgroundInvariant natural killer T (iNKT) cells produce copious amounts of cytokines in response to specific glycolipid antigens such as α-galactosylceramide (αGalCer) presented by CD1d-expressing antigen-presenting cells (APCs), thus orchestrating other immune cells to fight tumors. Because of their ability to induce strong antitumor responses activated by αGalCer, iNKT cells have been studied for their application in cancer immunotherapy. In our previous phase I/II trial in non-small cell lung cancer (NSCLC) patients who had completed the standard treatment, we showed a relatively long median survival time without severe treatment-related adverse events. Based on these results, we performed a phase II trial to evaluate clinical responses, safety profiles and immune responses as a second-line treatment for advanced NSCLC.MethodsPatients with advanced or recurrent NSCLC refractory to first-line chemotherapy were eligible. αGalCer-pulsed APCs were intravenously administered four times. Overall survival time was evaluated as the primary endpoint. The safety profile and immune responses after APC injection were also monitored. This study was an open label, single-arm, phase II clinical trial performed at Chiba University Hospital, Japan.ResultsThirty-five patients were enrolled in this study, of which 32 (91.4%) completed the trial. No severe adverse events related to the treatment were observed. The estimated median survival time of the 35 cases was 21.9 months (95% CI, 14.8 to 26.0). One case (2.9%) showed a partial response, 14 cases (40.0%) remained as stable disease, and 19 cases (54.3%) were evaluated as progressive disease. The geometric mean number of iNKT cells in all cases was significantly decreased and the mean numbers of natural killer (NK) cells, interferon-γ-producing cells in response to αGalCer, and effector CD8+ T cells were significantly increased after the administration of αGalCer-pulsed APCs.ConclusionsThe intravenous administration of αGalCer-pulsed APCs was well-tolerated and was accompanied by prolonged overall survival. These results are encouraging and warrant further evaluation in a randomized phase III trial to demonstrate the survival benefit of this immunotherapy.Trial registration numberUMIN000007321.
Phase 2 study of pembrolizumab in patients with advanced rare cancers
Authors: Naing Aung , Meric-Bernstam Funda , Stephen Bettzy , Karp Daniel D , Hajjar Joud , Rodon Ahnert Jordi , Piha-Paul Sarina A , Colen Rivka R , Jimenez Camilo , Raghav Kanwal P , Ferrarotto Renata , Tu Shi-Ming , Campbell Matthew , Wang Linghua , Sabir Sarjeel H , Tapia Coya , Bernatchez Chantale , Frumovitz Michael , Tannir Nizar , Ravi Vinod , Khan Saria , Painter Jeane M , Abonofal Abulrahman , Gong Jing , Alshawa Anas , McQuinn Lacey M , Xu Mingxuan , Ahmed Sara , Subbiah Vivek , Hong David S , Pant Shubham , Yap Timothy A , Tsimberidou Apostolia M , Dumbrava Ecaterina E Ileana , Janku Filip , Fu Siqing , Simon Richard M , Hess Kenneth R , Varadhachary Gauri R , Amir Habra Mouhammed 
Published: March 2020

BackgroundPatients with advanced rare cancers have poor prognosis and few treatment options. As immunotherapy is effective across multiple cancer types, we aimed to assess pembrolizumab (programmed cell death 1 (PD-1) inhibitor) in patients with advanced rare cancers.MethodsIn this open-label, phase 2 trial, patients with advanced rare cancers whose tumors had progressed on standard therapies, if available, within the previous 6 months were enrolled in nine tumor-specific cohorts and a 10th cohort for other rare histologies. Pembrolizumab 200 mg was administered intravenously every 21 days. The primary endpoint was non-progression rate (NPR) at 27 weeks; secondary endpoints were safety and tolerability, objective response rate (ORR), and clinical benefit rate (CBR).ResultsA total of 127 patients treated between August 15, 2016 and July 27, 2018 were included in this analysis. At the time of data cut-off, the NPR at 27 weeks was 28% (95% CI, 19% to 37%). A confirmed objective response (OR) was seen in 15 of 110 (14%) evaluable patients (complete response in one and partial response in 14). CBR, defined as the percentage of patients with an OR or stable disease ≥4 months, was 38% (n=42). Treatment was ongoing in 11 of 15 patients with OR at last follow-up. In the cohort with squamous cell carcinoma (SCC) of the skin, the NPR at 27 weeks was 36%, ORR 31%, and CBR 38%. In patients with adrenocortical carcinoma (ACC), NPR at 27 weeks was 31%, ORR 15%, and CBR 54%. In the patients with carcinoma of unknown primary (CUP), NPR at 27 weeks was 33%, ORR 23%, and CBR 54%. In the paraganglioma–pheochromocytoma cohort, NPR at 27 weeks was 43%, ORR 0%, and CBR 75%. Treatment-related adverse events (TRAEs) occurred in 66 of 127 (52%) patients, and 12 (9%) had grade ≥3 TRAEs. The most common TRAEs were fatigue (n=25) and rash (n=17). There were six deaths, all of which were unrelated to the study drug.ConclusionsThe favorable toxicity profile and antitumor activity seen in patients with SCC of skin, ACC, CUP, and paraganglioma–pheochromocytoma supports further evaluation of pembrolizumab in this patient population.Trial registration numberNCT02721732
Association of hyperlipidaemia with 5-year survival after hospitalisation for acute myocardial infarction: a propensity score matched analysis
Authors: Yousufuddin Mohammed , Zhu Ye , Al Ward Ruaa , Peters Jessica , Doyle Taylor , Jensen Kelsey L , Wang Zhen , Murad Mohammad Hassan 
Published: March 2020

ObjectivesThe primary objective was to examine the association between hyperlipidaemia (HLP) and 5-year survival after incident acute myocardial infarction (AMI). The secondary objectives were to assess the effect of HLP on survival to discharge across patient subgroups, and the impact of statin prescription, intensity and long-term statin adherence on 5-year survival.MethodsRetrospective cohort study of 7071 patients hospitalised for AMI at Mayo Clinic from 2001 through 2011. Of these, 2091 patients with HLP (age (mean±SD) 69.7±13.5) were propensity score matched to 2091 patients without HLP (age 70.6±14.2).ResultsIn matched patients, HLP was associated with higher rate of survival to discharge than no HLP (95% vs 91%; log-rank <0.0001). At year 5, the adjusted HR for all-cause mortality in patients with HLP versus no HLP was 0.66 (95% CI 0.58–0.74), and patients with prescription statin versus no statin was 0.24 (95% CI 0.21 to 0.28). The mean survival was 0.35 year greater in patients with HLP than in those with no HLP (95% CI 0.25 to 0.46). Patients with HLP gained on an average 0.17 life year and those treated with statin 0.67 life year at 5 years after AMI. The benefit of concurrent HLP was consistent across study subgroups.ConclusionsIn patients with AMI, concomitant HLP was associated with increased survival and a net gain in life years, independent of survival benefit from statin therapy. The results also reaffirm the role of statin prescription, intensity and adherence in reducing the mortality after incident AMI.
Isolated surgical tricuspid repair versus replacement: meta-analysis of 15 069 patients
Authors: Wang Tom Kai Ming , Griffin Brian P , Miyasaka Rhonda , Xu Bo , Popovic Zoran B , Pettersson Gosta B , Gillinov Alan Marc , Desai Milind Y 
Published: March 2020

ObjectivesTricuspid valve disease is increasingly encountered, but surgery is rarely performed in isolation, in part because of a reported higher operative risk than other single-valve operations. Although guidelines recommend valve repair, there is sparse literature for the optimal surgical approach in isolated tricuspid valve disease. We performed a meta-analysis examining outcomes of isolated tricuspid valve repair versus replacement.MethodsWe searched Pubmed, Embase, Scopus and Cochrane from January 1980 to June 2019 for studies reporting outcomes of both isolated tricuspid valve repair and replacement, excluding congenital tricuspid aetiologies. Data were extracted and pooled using random-effects models and Review Manager 5.3 software.ResultsThere were 811 article abstracts screened, from which 52 full-text articles reviewed and 16 studies included, totalling 6808 repairs and 8261 replacements. Mean age ranged from 36 to 68 years and females made up 24%–92% of these studies. Pooled operative mortality rates and odds ratios (95% confidence intervals) for isolated tricuspid repair and replacement surgery were 8.4% vs 9.9%, 0.80 (0.64 to 1.00). Tricuspid repair was also associated with lower in-hospital acute renal failure 12.4% vs 15.6%, 0.82 (0.72 to 0.93) and pacemaker implantation 9.4% vs 21.0%, 0.37 (0.24 to 0.58), but higher stroke rate 1.5% vs 0.9%, 1.63 (1.10 to 2.41). There were no differences in rates of prolonged ventilation, mediastinitis, return to operating room or late mortality.ConclusionIsolated tricuspid valve repair was associated with significantly reduced in-hospital mortality, renal failure and pacemaker implantation compared with replacement and is therefore recommended where feasible for isolated tricuspid valve disease, although its higher stroke rate warrants further research.
Death in low-risk cardiac surgery revisited
Authors: Lidén Katarina , Ivert Torbjörn , Sartipy Ulrik 
Published: March 2020

BackgroundA systematic review of low-risk death has been shown successful in identifying system weaknesses. The aim was to analyse early mortality in low-risk patients undergoing cardiac surgery and to determine the cause of death, classify if they were unavoidable or potentially preventable as a result of technical or system errors.MethodsWe included all low-risk patients who underwent cardiac surgery at our institution from 1 September 2009 to 31 August 2019. In patients operated between 2009 and 2011, we defined low risk as an additive European System for Cardiac Operative Risk Evaluation (EuroSCORE) I less than or equal to 3, and from 2012 and onwards as a EuroSCORE II less than or equal to 1.5. The medical records for the patients who died within 30 days of surgery were thoroughly examined and the cause of death was classified as cardiac or non-cardiac. Furthermore, deaths were categorised as not preventable, preventable (technical error) or preventable (system error).ResultsDuring the study period 3103 low-risk patients underwent surgery, and 11 patients died within 30 days of the operation (0.35%). Six of these (55%) were classified as preventable and five non-preventable. Four of the preventable deaths were classified as technical errors and two were due to system errors.ConclusionsA repeated systematic review of deaths in patients with a low preoperative risk showed that a majority of deaths were preventable, and therefore potentially avoidable. Similar to the previous assessment at our unit, mortality was very low and failure to communicate remains a modifiable factor that should be addressed.
Statefinder diagnosis for Tsallis agegraphic dark energy model with ωD − ωD′ pair
Authors: Srivastava Shikha , Dubey Vipin Chandra , Sharma Umesh Kumar 
Published: March 2020

A new class of dark energy model, known as “Tsallis agegraphic dark energy (TADE),” has been proposed using the holographic principle and Tsallis nonextensive entropy (Mod. Phys. Lett. A, 2019), considering the conformal time as well as the age of the Universe as IR cutoffs in flat Universe. The trajectories for evolution of statefinder parameters in [Formula: see text], [Formula: see text], [Formula: see text] and the [Formula: see text] planes are plotted for the TADE 1 and TADE 2 models for the value of the Tsallis parameter [Formula: see text], and taking the TADE energy density parameter [Formula: see text], according to the Planck 2018 results VI — [Formula: see text]CDM observational data without interaction.
AN ALTERNATIVE TO PERIODIC HOMOGENIZATION FOR DENTIN ELASTIC STIFFNESS
Authors: ARSON CHLOE , YASOTHAN YANNICK , JEANNERET ROMAIN , BENOIT AURELIE , ROUBIER NICOLAS , VENNAT ELSA 
Published: March 2020

Dentin, the main tissue of the tooth, is made of tubules surrounded by peri-tubular dentin (PTD), embedded in a matrix of inter-tubular dentin (ITD). The PTD and the ITD have different relative fractions of collagen and hydroxyapatite crystals. The ITD is typically less rigid than the PTD, which can be seen as a set of parallel hollow cylindrical reinforcements in the ITD matrix. In this paper, we extend Hashin and Rozen’s homogenization scheme to a nonuniform distribution of hollow PTD cylinders, determined from image analysis. We relate the transverse isotropic elastic coefficients of a Representative Elementary Volume (REV) of dentin to the elastic and topological properties of PTD and ITD. The model is calibrated against experimental data. Each sample tested is consistently characterized by Environmental Scanning Electron Microscopy (ESEM), nanoindentation and Resonant Ultrasound Spectroscopy (RUS), which ensures that macroscopic mechanical properties measured are correlated with microstructure observations. Despite the high variability of microstructure descriptors and mechanical properties, statistical analyses show that Hashin’s bounds converge and that the proposed model can be used for back-calculating the microscopic Poisson’s ratios of dentin constituents. Three-point bending tests conducted in the laboratory were simulated with the Finite Element Method (FEM). Elements were assigned transverse isotropic elastic parameters calculated by homogenization. The tubule orientation and the pdf of the ratio inner/outer tubule radius were determined in several zones of the beams before testing. The remainder of the micro-mechanical parameters were taken equal to those calibrated by RUS. The horizontal strains found experimentally by Digital Image Correlation (DIC) were compared to those found by FEM. The DIC and FEM horizontal strain fields showed a very good agreement in trend and order of magnitude, which verifies the calibration of the homogenization model. By contrast with previous studies of dentin, we fully calibrated a closed form mechanical model against experimental data and we explained the testing procedures. In elastic conditions, the proposed homogenization scheme gives a better account of microstructure variability than micro–macro dentin models with periodic microstructure.
The StoryTeller
Authors: Elbakly Rizanne , Youssef Moustafa 
Published: March 2020

Due to the recent proliferation of location-based services indoors, the need for an accurate floor estimation technique that is easy to deploy in any typical multi-story building is higher than ever. Current approaches that attempt to solve the floor localization problem include sensor-based systems and 3D fingerprinting. Nevertheless, these systems incur high deployment and maintenance overhead, suffer from sensor drift and calibration issues, and/or are not available to all users.
In this paper, we propose StoryTeller, a deep learning-based technique for floor prediction in multi-story buildings. StoryTeller leverages the ubiquitous WiFi signals to generate images that are input to a Convolutional Neural Network (CNN) which is trained to predict loors based on detected patterns in visible WiFi scans. Input images are created such that they capture the current WiFi-scan in an AP-independent manner. In addition, a novel virtual building concept is used to normalize the information in order to make them building-independent. This allows StoryTeller to reuse a trained network for a completely new building, significantly reducing the deployment overhead.
We have implemented and evaluated StoryTeller using three different buildings with a side-by-side comparison with the state-of-the-art floor estimation techniques. The results show that StoryTeller can estimate the user's floor at least 98.3% within one floor of the actual ground truth floor. This accuracy is consistent across the different testbeds and for scenarios where the models used were trained in a completely different building than the tested building. This highlights StoryTeller's ability to generalize to new buildings and its promise as a scalable, low-overhead, high-accuracy floor localization system.
CARIN
Authors: Bai Yunhao , Wang Xiaorui 
Published: March 2020

Recent studies have proposed to use the Channel State Information (CSI) of WiFi wireless channel for human gesture recognition. As an important application, CSI-based driver activity recognition in passenger vehicles has received increasing research attention. However, a serious limitation of almost all the existing WiFi-based recognition solutions is that they can only recognize the activity of a single person at a time, because the activities of other people (if performed at the same time) can interfere with the WiFi signals. In a sharp contrast, there can often be one or more passengers in any vehicles.
In this paper, we propose CARIN, CSI-based driver Activity Recognition under the INterference of passengers. CARIN features a combination-based solution that profiles all the possible activity combinations of driver and (one or more) passengers in offline training and then performs recognition online. To attack possible combination explosion, we first leverage in-car pressure sensors to significantly reduce combinations, because there are only limited seating options in a passenger vehicle. We then formulate a distance minimization problem for fast runtime recognition. In addition, a period analysis methodology is designed based on the kNN classifier to recognize activities that have a sequence of body movements, like continuous head nodding due to driver fatigue. Our results in a real car with 3,000 real-world traces show that CARIN can achieve an overall F1 score of 90.9%, and outperforms the three state-of-the-art solutions by 32.2%.
Noncoding Variants Connect Enhancer Dysregulation with Nuclear Receptor Signaling in Hematopoietic Malignancies
Authors: Li Kailong , Zhang Yuannyu , Liu Xin , Liu Yuxuan , Gu Zhimin , Cao Hui , Dickerson Kathryn E. , Chen Mingyi , Chen Weina , Shao Zhen , Ni Min , Xu Jian 
Published: March 2020

Abstract

Mutations in protein-coding genes are well established as the basis for human cancer, yet how alterations within noncoding genome, a substantial fraction of which contain cis-regulatory elements (CRE), contribute to cancer pathophysiology remains elusive. Here, we developed an integrative approach to systematically identify and characterize noncoding regulatory variants with functional consequences in human hematopoietic malignancies. Combining targeted resequencing of hematopoietic lineage–associated CREs and mutation discovery, we uncovered 1,836 recurrently mutated CREs containing leukemia-associated noncoding variants. By enhanced CRISPR/dCas9–based CRE perturbation screening and functional analyses, we identified 218 variant-associated oncogenic or tumor-suppressive CREs in human leukemia. Noncoding variants at KRAS and PER2 enhancers reside in proximity to nuclear receptor (NR) binding regions and modulate transcriptional activities in response to NR signaling in leukemia cells. NR binding sites frequently colocalize with noncoding variants across cancer types. Hence, recurrent noncoding variants connect enhancer dysregulation with nuclear receptor signaling in hematopoietic malignancies.

Significance:
We describe an integrative approach to identify noncoding variants in human leukemia, and reveal cohorts of variant-associated oncogenic and tumor-suppressive cis-regulatory elements including KRAS and PER2 enhancers. Our findings support a model in which noncoding regulatory variants connect enhancer dysregulation with nuclear receptor signaling to modulate gene programs in hematopoietic malignancies.
See related commentary by van Galen, p. 646.
This article is highlighted in the In This Issue feature, p. 627
Effectiveness of Fingolimod versus Natalizumab as Second-Line Therapy for Relapsing-Remitting Multiple Sclerosis in Spain: Second-Line GATE Study
Authors: Meca-Lallana José , Ayuso Teresa , Martínez-Yelamos Sergio , Durán Carmen , Contreras Martín Yessica , Herrera Navarro Nicolás , Pérez Sempere Angel , Álvarez-Cermeño Jose C. , Millán Pascual Jorge , Meca-Lallana Virginia , Romero Sevilla Raúl , Ricart Javier 
Published: March 2020

<b><i>Background:</i></b> There is a lack of head-to-head studies comparing the efficacy of fingolimod (FIN) and natalizumab (NTZ) as second-line therapy for relapsing-remitting multiple sclerosis (RRMS). <b><i>Methods:</i></b> Multicenter, observational study, in which, information of 388 patients randomly selected and treated with FIN or NTZ in routine clinical practice was retrospectively collected with the main objective of comparing the annualized relapse rate (ARR) over the first year, after FIN or NTZ treatment initiation. <b><i>Results:</i></b> Mean ARR during the first year of treatment was 0.28 in FIN group and 0.12 in NTZ group (<i>p</i> = 0.0064); nevertheless, the difference between groups lost statistical significance when the propensity score analysis was performed. Time to disability ­progression was similar in both treatment groups (12.3 ± 6.7 months in FIN, and 12.8 ± 0.1 months in NTZ; <i>p</i> = 0.4654). Treatment persistence after the first year of treatment was higher in patients treated with FIN (95%) than in those treated with NTZ (84%; <i>p</i> = 0.0014). <b><i>Conclusions:</i></b> After 12 months of treatment, both FIN and NTZ reduced the ARR, but ARR percent reduction was significantly higher with NTZ. Treatment persistence was higher in patients receiving FIN.
Activated Platelets Induce Endothelial Cell Inflammatory Response in Psoriasis via COX-1
Authors: Garshick Michael S. , Tawil Michael , Barrett Tessa J. , Salud-Gnilo Charissa M. , Eppler Michael , Lee Angela , Scher Jose U. , Neimann Andrea L. , Jelic Sanja , Mehta Nehal N. , Fisher Edward A. , Krueger James G. , Berger Jeffrey S. 
Published: March 2020

Objective:
Patients with psoriasis have impaired vascular health and increased cardiovascular disease (CVD). Platelets are key players in the pathogenesis of vascular dysfunction in cardiovascular disease and represent therapeutic targets in cardiovascular prevention. The object of this study was to define the platelet phenotype and effector cell properties on vascular health in psoriasis and evaluate whether aspirin modulates the platelet-induced phenotype.

Approach and Results:

Platelets from psoriasis patients (n=45) exhibited increased platelet activation (relative to age- and gender-matched controls, n=18), which correlated with psoriasis skin severity. Isolated platelets from psoriasis patients demonstrated a 2- to 3-fold (
P
<0.01) increased adhesion to human aortic endothelial cells and induced proinflammatory transcriptional changes, including upregulation of
IL 8
(interleukin 8),
IL1β
, and Cox (cyclooxygenase)-2 Platelet RNA sequencing revealed an interferon signature and elevated expression of
COX-1
, which correlated with psoriasis disease severity (
r
=0.83,
P
=0.01). In a randomized trial of patients with psoriasis, 2 weeks of 81 mg low-dose aspirin, a COX-1 inhibitor, reduced serum thromboxane (Tx) B
2
and reduced brachial vein endothelial proinflammatory transcript expression >70% compared with the no-treatment group (
P
<0.01). Improvement in brachial vein endothelial cell inflammation significantly correlated with change in serum TxB
2
(
r
=0.48,
P
=0.02).

Conclusions:
In patients with psoriasis, platelets are activated and induce endothelial cell inflammation. Low-dose aspirin improved endothelial cell health in psoriasis via platelet COX-1 inhibition. These data demonstrate a previously unappreciated role of platelets in psoriasis and endothelial cell inflammation and suggests that aspirin may be effective in improving vascular health in patients with psoriasis.

Registration:

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT03228017.