bluuebunny/crossref_metadata_2025_split huggingface dataset:
Temporal changes in the documentation of neurological findings among patients with acute ischaemic stroke in a single centre in Japan: a retrospective cross-sectional study
Authors: Komagamine Junpei , Komagamine Tomoko 
Published: December 2017

ObjectiveTo evaluate temporal differences in the documentation of neurological findings by the same physicians in patients with ischaemic stroke while in hospital. We also investigated differences in the rate of documentation of neurological findings in patients with stroke between internists and neurosurgeons.DesignA retrospective medical chart review.ParticipantsHospitalised adult patients with acute ischaemic stroke who stayed 7 or more days in our hospital. Neurosurgeons (n=8) and internists (n=19) caring for these patients (including up to 10 patients per physician).Main outcome measuresThe documentation rate of any neurological finding in the patients on each day (from day 1 to 7 and on discharge). The documentation rates of eight neurological finding components (consciousness, mental status, cranial nerves, motor function, sensory function, coordination, reflexes and gait). We included only documentation by the same physician. Fisher’s exact test was used to evaluate differences in outcomes between neurosurgeons and internists.ResultsDuring the study period, we identified 172 patients with stroke who were cared for by 27 physicians. The documentation rates of any neurological findings were 94% (day 1), 58% (day 2), 35% (day 3), 40% (day 4), 32% (day 5), 30% (day 6) and 23% (day 7). On discharge, all eight neurological finding components were documented in less than 10% of all cases. The documentation rate was significantly higher by internists than that by neurosurgeons on each day but not on discharge.ConclusionsThe documentation rate of neurological findings by physicians during usual stroke care decreased to less than 50% after the third hospital day. Given the importance of temporal changes in the neurological symptoms of patients with stroke, further study is needed to determine whether this low documentation rate after the third hospital day was due to a lack of physician interest in neurological findings or other factors.
Parameterized Testability
Authors: Iwama Kazuo , Yoshida Yuichi 
Published: December 2017

This article studies property testing for NP optimization problems with parameter
k
under the general graph model with an augmentation of random edge sampling capability. It is shown that a variety of such problems, including
k
-Vertex Cover,
k
-Feedback Vertex Set,
k
-Multicut,
k
-Path-Free, and
k
-Dominating Set, are constant-query testable if
k
is constant. It should be noted that the first four problems are fixed parameter tractable (FPT) and it turns out that algorithmic techniques for their FPT algorithms (branch-and-bound search, color coding, etc.) are also useful for our testers.
k
-Dominating Set is
W
[2]-hard, but we can still test the property with a constant number of queries, since the definition of ε-farness makes the problem trivial for non-sparse graphs that are the source of hardness for the original optimization problem. We also consider
k
-Odd Cycle Transversal, which is another well-known FPT problem, but we only give a sublinear-query tester when
k
is a constant.
Ipilimumab plus Lenalidomide after Allogeneic and Autologous Stem Cell Transplantation for Patients with Lymphoid Malignancies
Authors: Khouri Issa F. , Fernandez Curbelo Irina , Turturro Francesco , Jabbour Elias J. , Milton Denái R. , Bassett Roland L. , Vence Luis M. , Allison James P. , Gulbis Alison M. , Sharma Padmanee 
Published: December 2017

Abstract
Purpose: Prevention or treatment of relapsed lymphoid malignancies after hematopoietic stem cell transplantation (HSCT) requires novel strategies. We hypothesized that antitumor–cell responses could be enhanced by the addition of lenalidomide to the cytotoxic T-lymphocyte–associated protein 4 inhibitor ipilimumab.
Experimental Design: We conducted a phase II investigator-initiated trial to assess the safety and activity of ipilimumab and lenalidomide in patients with lymphoid malignancies that relapsed after allogeneic HSCT and in high-risk patients after autologous HSCT. Patients received 10 mg of oral lenalidomide daily for 21 days followed by intravenous ipilimumab at 3 mg/kg bodyweight. The regimen was repeated 4 weeks later for a total of four treatments.
Results: We enrolled 17 patients (10 allogeneic and seven autologous transplant recipients). Immune-mediated toxicity was limited to one patient with asymptomatic hypothyroidism and one with dermatitis in the allogeneic and autologous groups, respectively. One allogeneic transplant recipient had a flare of prior GVHD while taking lenalidomide that precluded further treatment. All others finished treatment without GVHD. Four of 10 patients in the allogeneic group had complete responses (three of which were durable at 19+, 21+, and 32+ months), and three had partial responses. The disease in six of seven patients in the autologous group remains in remission. The groups had similar immune responses, including a two- to threefold increase in inducible ICOS+CD4+FoxP3− T-cell number.
Conclusions: Our early-phase data suggested that ipilimumab plus lenalidomide is well tolerated after HSCT. Adverse events did not differ significantly between the allogeneic and autologous groups. Clin Cancer Res; 24(5); 1011–8. ©2017 AACR.
Afatinib Is a New Therapeutic Approach in Chordoma with a Unique Ability to Target EGFR and Brachyury
Authors: Magnaghi Paola , Salom Barbara , Cozzi Liviana , Amboldi Nadia , Ballinari Dario , Tamborini Elena , Gasparri Fabio , Montagnoli Alessia , Raddrizzani Laura , Somaschini Alessio , Bosotti Roberta , Orrenius Christian , Bozzi Fabio , Pilotti Silvana , Galvani Arturo , Sommer Josh , Stacchiotti Silvia , Isacchi Antonella 
Published: December 2017

Abstract
Chordomas are rare bone tumors with no approved therapy. These tumors express several activated tyrosine kinase receptors, which prompted attempts to treat patients with tyrosine kinase inhibitors. Although clinical benefit was observed in phase II clinical trials with imatinib and sorafenib, and sporadically also with EGFR inhibitors, therapies evaluated to date have shown modest activity. With the goal of identifying new drugs with immediate therapeutic potential for chordoma patients, we collected clinically approved drugs and other advanced inhibitors of MET, PDGFRβ, and EGFR tyrosine kinases, and assessed their antiproliferative activity against a panel of chordoma cell lines. Chordoma cell lines were not responsive to MET and PDGFRβ inhibitors. U-CH1 and UM-Chor1 were sensitive to all EGFR inhibitors, whereas the remaining cell lines were generally insensitive to these drugs. Afatinib was the only EGFR inhibitor with activity across the chordoma panel. We then investigated the molecular mechanisms behind the responses observed and found that the antiproliferative IC50s correlate with the unique ability of afatinib to promote degradation of EGFR and brachyury, an embryonic transcription factor considered a key driver of chordoma. Afatinib displayed potent antitumor efficacy in U-CH1, SF8894, CF322, and CF365 chordoma tumor models in vivo. In the panel analyzed, high EGFR phosphorylation and low AXL and STK33 expression correlated with higher sensitivity to afatinib and deserve further investigation as potential biomarkers of response. These data support the use of afatinib in clinical trials and provide the rationale for the upcoming European phase II study on afatinib in advanced chordoma. Mol Cancer Ther; 17(3); 603–13. ©2017 AACR.
Molecularly Targeted Cancer Combination Therapy with Near-Infrared Photoimmunotherapy and Near-Infrared Photorelease with Duocarmycin–Antibody Conjugate
Authors: Nagaya Tadanobu , Gorka Alexander P. , Nani Roger R. , Okuyama Shuhei , Ogata Fusa , Maruoka Yasuhiro , Choyke Peter L. , Schnermann Martin J. , Kobayashi Hisataka 
Published: December 2017

Abstract
Near-infrared photoimmunotherapy (NIR-PIT) is a highly selective tumor treatment that uses an antibody–photoabsorber conjugate (APC). However, the effect of NIR-PIT can be enhanced when combined with other therapies. NIR photocaging groups, based on the heptamethine cyanine scaffold, have been developed to release bioactive molecules near targets after exposure to light. Here, we investigated the combination of NIR-PIT using panitumumab–IR700 (pan-IR700) and the NIR-releasing compound, CyEt–panitumumab–duocarmycin (CyEt-Pan-Duo). Both pan-IR700 and CyEt-Pan-Duo showed specific binding to the EGFR-expressing MDAMB468 cell line in vitro. In in vivo studies, additional injection of CyEt-Pan-Duo immediately after NIR light exposure resulted in high tumor accumulation and high tumor–background ratio. To evaluate the effects of combination therapy in vivo, tumor-bearing mice were separated into 4 groups: (i) control, (ii NIR-PIT, (iii) NIR-release, (iv) combination of NIR-PIT and NIR-release. Tumor growth was significantly inhibited in all treatment groups compared with the control group (P &lt; 0.05), and significantly prolonged survival was achieved (P &lt; 0.05 vs. control). The greatest therapeutic effect was shown with NIR-PIT and NIR-release combination therapy. In conclusion, combination therapy of NIR-PIT and NIR-release enhanced the therapeutic effects compared with either NIR-PIT or NIR-release therapy alone. Mol Cancer Ther; 17(3); 661–70. ©2017 AACR.
Persistence of Infarct Zone T2 Hyperintensity at 6 Months After Acute ST-Segment–Elevation Myocardial Infarction
Authors: Carberry Jaclyn , Carrick David , Haig Caroline , Ahmed Nadeem , Mordi Ify , McEntegart Margaret , Petrie Mark C. , Eteiba Hany , Hood Stuart , Watkins Stuart , Lindsay Mitchell , Davie Andrew , Mahrous Ahmed , Ford Ian , Sattar Naveed , Welsh Paul , Radjenovic Aleksandra , Oldroyd Keith G. , Berry Colin 
Published: December 2017

Background—
The incidence and clinical significance of persistent T2 hyperintensity after acute ST-segment–elevation myocardial infarction (STEMI) is uncertain.

Methods and Results—

Patients who sustained an acute STEMI were enrolled in a cohort study (BHF MR-MI: NCT02072850). Two hundred eighty-three STEMI patients (mean age, 59±12 years; 75% male) had cardiac magnetic resonance with T2 mapping performed at 2 days and 6 months post-STEMI. Persisting T2 hyperintensity was defined as infarct T2 >2 SDs from remote T2 at 6 months. Infarct zone T2 was higher than remote zone T2 at 2 days (66.3±6.1 versus 49.7±2.1 ms;
P
<0.001) and 6 months (56.8±4.5 versus 49.7±2.3 ms;
P
<0.001). Remote zone T2 did not change over time (mean change, 0.0±2.7 ms;
P
=0.837), whereas infarct zone T2 decreased (−9.5±6.4 ms;
P
<0.001). At 6 months, T2 hyperintensity persisted in 189 (67%) patients, who were more likely to have Thrombus in Myocardial Infarction flow 0 or 1 in the culprit artery (
P
=0.020), incomplete ST-segment resolution (
P
=0.037), and higher troponin (
P
=0.024). Persistent T2 hyperintensity was associated with NT-proBNP (N-terminal pro-B-type natriuretic peptide) concentration (0.57 on a log scale [0.42–0.72];
P
=0.004) and the likelihood of adverse left ventricular remodeling (>20% change in left ventricular end-diastolic volume; 21.91 [2.75–174.29];
P
=0.004). Persistent T2 hyperintensity was associated with all-cause death and heart failure, but the result was not significant (
P
=0.051). ΔT2 was associated with all-cause death and heart failure (
P
=0.004) and major adverse cardiac events (
P
=0.013).

Conclusions—
Persistent T2 hyperintensity occurs in two thirds of STEMI patients. Persistent T2 hyperintensity was associated with the initial STEMI severity, adverse remodeling, and long-term health outcome.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT02072850.
Nativity Status and Cardiovascular Disease Mortality Among Hispanic Adults
Authors: Rodriguez Fatima , Hastings Katherine G. , Hu Jiaqi , Lopez Lenny , Cullen Mark , Harrington Robert A. , Palaniappan Latha P. 
Published: December 2017

BackgroundHispanic persons represent a heterogeneous and growing population of any race with origins in Mexico, the Caribbean, Central America, South America, or other Spanish‐speaking countries. Previous studies have documented variation in cardiovascular risk and outcomes among Hispanic subgroups. Few studies have investigated whether these patterns vary by nativity status among Hispanic subgroups.Methods and ResultsWe used the National Center for Health Statistics mortality file to compare deaths of Hispanic (n=1 258 229) and non‐Hispanic white (n=18 149 774) adults (aged ≥25 years) from 2003 to 2012. We identified all deaths related to cardiovascular disease (CVD) and categorized them by subtype (allCVD, ischemic, or cerebrovascular) using the underlying cause of death (International Classification of Diseases, 10th Revisioncodes I00–I78, I20–I25, and I60–I69, respectively). Population estimates were calculated using linear interpolation from the 2000 and 2010 US censuses.CVDaccounted for 31% of all deaths among Hispanic adults. Race/ethnicity and nativity status were recorded on death certificates by the funeral director using state guidelines. Nativity status was defined as foreign versus US born; 58% of Hispanic decedents were foreign born. Overall, Hispanic adults had lower age‐adjustedCVDmortality rates than non‐Hispanic white adults (296 versus 385 per 100 000). Foreign‐born Cubans, Mexicans, and Puerto Ricans had higherCVDmortality than their US‐born counterparts (rate ratio: 2.64 [95% confidence interval, 2.46–2.81], 1.17 [95% confidence interval, 1.15–1.21], and 1.91 [95% confidence interval, 1.83–1.99], respectively).ConclusionsMortality rates for total cardiovascular, ischemic, and cerebrovascular disease are higher among foreign‐ than US‐born Hispanic adults. These findings suggest the importance of disaggregatingCVDmortality by disease subtype, Hispanic subgroup, and nativity status.
The Role and Place of ‘Commodity Fetishism’ in Marx’s Systematic-dialectical Exposition in Capital
Authors: Starosta Guido 
Published: December 2017

AbstractThis article aims to contribute to the literature on Marx’s systematic-dialectical method through a critical reading and discussion of the significance and presentational ‘architecture’ of the section on commodity fetishism in the dialectical sequence of form-determinations inCapital. In order to undertake this task, the paper firstly explores the content and expositional structure of the first three sections of Chapter 1 ofCapital. This sets the stage for a methodologically-minded close examination of Marx’s presentation of the fetish character of the commodity, which shows that there is a precise systematic sequence which gives unity to the flow of his argument within the section on ‘The Fetishism of the Commodity and its Secret’. The conclusion is that only through a proper grasp of the dialectical method can the full systematic significance and implications of Marx’s account of commodity fetishism be uncovered.
Mutagenicity evaluation ofAnastatica hierochunticaL. aqueous extractin vitroandin vivo
Authors: Md Zin Siti Rosmani , Mohamed Zahurin , Alshawsh Mohammed A , Wong Won F , Kassim Normadiah M 
Published: December 2017

Anastatica hierochuntica L. ( A. hierochuntica), a folk medicinal plant, was evaluated for mutagenic potential via in vitro and in vivo assays. The in vitro assay was conducted according to modified Ames test, while the in vivo study was performed according to Organisation for Economic Co-operation and Development guideline for mammalian erythrocyte micronucleus assay. Four groups ( n= 5 males and 5 females per group) Sprague Dawley rats were randomly chosen as the negative control, positive control (received a single intramuscular injection of cyclophosphamide 50 mg/kg), 1000 and, 2000 mg/kg A. hierochuntica aqueous extracts. All groups except the positive control were treated orally for three days. Findings of the in vitro assay showed mutagenic potential of AHAE at 0.04 and 0.2 mg/ml. However, no mutagenic effect was demonstrated in the in vivo study up to 2000 mg/kg. No significant reduction in the polychromatic and normochromatic erythrocytes ratio was noted in any of the groups. Meanwhile, high micronucleated polychromatic erythrocytes frequency was seen in cyclophosphamide-treated group only. These findings could perhaps be due to insufficient dosage of A. hierochuntica aqueous extracts to cause genetic damage on the bone marrow target cells. Further acute and chronic in vivo toxicity studies may be required to draw pertinent conclusion on the safety aspect of A. hierochuntica aqueous extracts consumption.Impact statementIn this paper, we report on the mutagenicity evaluation of Anastatica hierochuntica aqueous extract. This is a significant research in view of the popularity of this herb consumption by the people across the globe despite of limited scientific evidence on its toxicity potential. This study is intended to encourage more extensive related research in order to provide sufficient evidence and guidance for determining its safe dosage.
Prognostic value of right ventricular dilatation in patients with low-risk pulmonary embolism
Authors: Côté Benoit , Jiménez David , Planquette Benjamin , Roche Anne , Marey Jonathan , Pastré Jean , Meyer Guy , Sanchez Olivier 
Published: December 2017

The prognosis of multidetector computed tomography (MDCT) assessed right ventricular dilatation (RVD) is unclear in patients with pulmonary embolism (PE) and a simplified Pulmonary Embolism Severity Index (sPESI) of 0. We investigated in these patients whether MDCT-assessed RVD, defined by a right to left ventricular ratio (RV/LV) ≥0.9 or ≥1.0, is associated with worse outcomes.We combined data from three prospective cohorts of patients with PE. The main study outcome was the composite of 30-day all-cause mortality, haemodynamic collapse or recurrent PE in patients with sPESI of 0.Among 779 patients with a sPESI 0, 420 (54%) and 299 (38%) had a RV/LV ≥0.9 and ≥1.0 respectively. No difference in primary outcome was observed, 0.95% (95% CI 0.31–2.59)versus0.56% (95% CI 0.10–2.22; p=0.692) and 1.34% (95% CI 0.43–3.62)versus0.42% (95% CI 0.07–1.67; p=0.211) with RV/LV ≥0.9 and ≥1.0 respectively. Increasing the RV/LV threshold to ≥1.1, the outcome occurred more often in patients with RVD (2.12%, 95% CI 0.68–5.68versus0.34%, 95% CI 0.06–1.36; p=0.033).MDCT RV/LV ratio of ≥0.9 and ≥1.0 in sPESI 0 patients is frequent but not associated with a worse prognosis but higher cut-off values might be associated with worse outcome in these patients.
Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor–Positive Metastatic Breast Cancer: ALTERNATIVE
Authors: Johnston Stephen R.D. , Hegg Roberto , Im Seock-Ah , Park In Hae , Burdaeva Olga , Kurteva Galina , Press Michael F. , Tjulandin Sergei , Iwata Hiroji , Simon Sergio D. , Kenny Sarah , Sarp Severine , Izquierdo Miguel A. , Williams Lisa S. , Gradishar William J. 
Published: December 2017

Purpose Human epidermal growth factor receptor 2 (HER2) targeting plus endocrine therapy (ET) improved clinical benefit in HER2-positive, hormone receptor (HR)–positive metastatic breast cancer (MBC) versus ET alone. Dual HER2 blockade enhances clinical benefit versus single HER2 blockade. The ALTERNATIVE study evaluated the efficacy and safety of dual HER2 blockade plus aromatase inhibitor (AI) in postmenopausal women with HER2-positive/HR-positive MBC who received prior ET and prior neo(adjuvant)/first-line trastuzumab (TRAS) plus chemotherapy. Methods Patients were randomly assigned (1:1:1) to receive lapatinib (LAP) + TRAS + AI, TRAS + AI, or LAP + AI. Patients for whom chemotherapy was intended were excluded. The primary end point was progression-free survival (PFS; investigator assessed) with LAP + TRAS + AI versus TRAS + AI. Secondary end points were PFS (comparison of other arms), overall survival, overall response rate, clinical benefit rate, and safety. Results Three hundred fifty-five patients were included in this analysis: LAP + TRAS + AI (n = 120), TRAS + AI (n = 117), and LAP + AI (n = 118). Baseline characteristics were balanced. The study met its primary end point; superior PFS was observed with LAP + TRAS + AI versus TRAS + AI (median PFS, 11 v 5.7 months; hazard ratio, 0.62; 95% CI, 0.45 to 0.88; P = .0064). Consistent PFS benefit was observed in predefined subgroups. Overall response rate, clinical benefit rate, and overall survival also favored LAP + TRAS + AI. The median PFS with LAP + AI versus TRAS + AI was 8.3 versus 5.7 months (hazard ratio, 0.71; 95% CI, 0.51 to 0.98; P = .0361). Common adverse events (AEs; ≥ 15%) with LAP + TRAS + AI, TRAS + AI, and LAP + AI were diarrhea (69%, 9%, and 51%, respectively), rash (36%, 2%, and 28%, respectively), nausea (22%, 9%, and 22%, respectively), and paronychia (30%, 0%, and 15%, respectively), mostly grade 1 or 2. Serious AEs were reported similarly across the three groups, and AEs leading to discontinuation were lower with LAP + TRAS + AI. Conclusion Dual HER2 blockade with LAP + TRAS + AI showed superior PFS benefit versus TRAS + AI in patients with HER2-positive/HR-positive MBC. This combination offers an effective and safe chemotherapy-sparing alternative treatment regimen for this patient population.
Photoreceptor signalling is sufficient to explain the detectability threshold of insect aerial pursuers
Authors: Rigosi Elisa , Wiederman Steven D. , O'Carroll David C. 
Published: December 2017

ABSTRACTAn essential biological task for many flying insects is the detection of small, moving targets, such as when pursuing prey or conspecifics. Neural pathways underlying such ‘target-detecting’ behaviours have been investigated for their sensitivity and tuning properties (size, velocity). However, which stage of neuronal processing limits target detection is not yet known. Here, we investigated several skilled, aerial pursuers (males of four insect species), measuring the target-detection limit (signal-to-noise ratio) of light-adapted photoreceptors. We recorded intracellular responses to moving targets of varying size, extended well below the nominal resolution of single ommatidia. We found that the signal detection limit (2× photoreceptor noise) matches physiological or behavioural target-detection thresholds observed in each species. Thus, across a diverse range of flying insects, individual photoreceptor responses to changes in light intensity establish the sensitivity of the feature detection pathway, indicating later stages of processing are dedicated to feature tuning, tracking and selection.