bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel, single-beat approach for determining both end-systolic pressure–dimension relationship and preload recruitable stroke work
Authors: Inuzuka Ryo , Kass David A , Senzaki Hideaki 
Published: June 2016

ObjectiveThe end-systolic pressure–dimension relationship (ESPDR) and the preload recruitable stroke work (PRSW) relationship are load-insensitive measures of contractility, but their clinical application has been limited by the need to record multiple beats over a wide volume range. In this study, we therefore sought to validate a new method to concomitantly determine the ESPDR and the PRSW relationship from a single beat.MethodsPressure–dimension loops were recorded in 14 conscious dogs under various haemodynamic and pathological conditions. Multiple-beat PRSW relationship was determined for its slope (Mw) and for a dimension-axis intercept (Dw). The ESPDR represented by the formula, was estimated from a steady-state, single-beat late-systolic pressure–dimension relationship. The single-beat Mwwas determined as an end-systolic pressure when the end-systolic dimension was equal to Dw.ResultsA strong correlation was observed between multiple-beat and single-beat ESPDRs (zero-stress dimension; r=0.98, p<0.0001). The single-beat estimation of Mwcalculated using the wall thickness was strongly correlated with the actual Mw(r=0.93, p<0.0001) and was sensitive enough to detect the change in contractility by dobutamine infusion (p<0.001) and by tachycardia-induced heart failure (p<0.001). Similar results were obtained for Mwestimated without information on wall thickness.ConclusionsMwcan be interpreted as an end-systolic pressure when the end-systolic dimension is equal to Dw. By using the non-linear ESPDR, accurate single-beat estimation of the ESPDR and Mwis possible even without information on wall thickness. These results should enhance the applicability of pressure–volume framework to clinical medicine.
Way-out to the gravitino problem in intersecting D-brane Pati–Salam models
Authors: Addazi Andrea , Khlopov Maxim Yu 
Published: June 2016

We discuss the gravitino problem in the context of the exotic see-saw mechanism for neutrinos and leptogenesis, UV completed by intersecting D-branes Pati–Salam models. In the exotic see-saw model, supersymmetry is broken at high scales M[Formula: see text] 109 GeV and this seems in contradiction with gravitino bounds from inflation and baryogenesis. However, if gravitino is the lightest stable supersymmetric particle, it will not decay into other SUSY particles, avoiding the gravitino problem and providing a good cold dark matter (CDM). Gravitini are super heavy dark particles and they can be produced by non-adiabatic expansion during inflation. Intriguingly, from bounds on the correct abundance of dark matter (DM), we also constrain the neutrino sector. We set a limit on the exotic instantonic coupling of [Formula: see text] 10[Formula: see text]–10[Formula: see text]. This also sets constrains on the Calabi–Yau compactifications and on the string scale. This model strongly motivates very high energy DM indirect detection of neutrini and photons of 10[Formula: see text]–10[Formula: see text] GeV: gravitini can decay on them in a cosmological time because of soft R-parity breaking effective operators.
Ultralow frequency acoustic bandgap and vibration energy recovery in tetragonal folding beam phononic crystal
Authors: Gao Nansha , Wu Jiu Hui , Yu Lie , Hou Hong 
Published: June 2016

This paper investigates ultralow frequency acoustic properties and energy recovery of tetragonal folding beam phononic crystal (TFBPC) and its complementary structure. The dispersion curve relationships, transmission spectra and displacement fields of the eigenmodes are studied with FEA in detail. Compared with the traditional three layer phononic crystal (PC) structure, this structure proposed in this paper not only unfold bandgaps (BGs) in lower frequency range (below 300 Hz), but also has lighter weight because of beam structural cracks. We analyze the relevant physical mechanism behind this phenomenon, and discuss the effects of the tetragonal folding beam geometric parameters on band structure maps. FEM proves that the multi-cell structures with different arrangements have different acoustic BGs when compared with single cell structure. Harmonic frequency response and piezoelectric properties of TFBPC are specifically analyzed. The results confirm that this structure does have the recovery ability for low frequency vibration energy in environment. These conclusions in this paper could be indispensable to PC practical applications such as BG tuning and could be applied in portable devices, wireless sensor, micro-electro mechanical systems which can recycle energy from vibration environment as its own energy supply.
Sorafenib and Quinacrine Target Anti-Apoptotic Protein MCL1: A Poor Prognostic Marker in Anaplastic Thyroid Cancer (ATC)
Authors: Abdulghani Junaid , Gokare Prashanth , Gallant Jean-Nicolas , Dicker David , Whitcomb Tiffany , Cooper Timothy , Liao Jiangang , Derr Jonathan , Liu Jing , Goldenberg David , Finnberg Niklas K. , El-Deiry Wafik S. 
Published: June 2016

Abstract
Purpose and Experimental Design: Anaplastic thyroid cancer (ATC) comprises approximately 2% of all thyroid cancers, and its median survival rate remains poor. It is responsible for more than one third of thyroid cancer–related deaths. ATC is frequently resistant to conventional therapy, and NFκB signaling has been proposed to be a feature of the disease. We aimed to assess the activity of the antimalaria drug quinacrine known to target NFκB signaling in combination with the clinically relevant kinase inhibitor sorafenib in ATC cells. The presence of NFκB-p65/RELA and its target MCL1 was demonstrated in ATC by meta-data gene set enrichment analysis and IHC. We assessed the responses of a panel of human ATC cell lines to quinacrine and sorafenib in vitro and in vivo.
Results: We detected increased expression of NFκB-p65/RELA and MCL1 in the nucleus of a subset of ATC compared with non-neoplastic thyroid. ATC cells were found to respond with additive/synergistic tumor cell killing to the combination of sorafenib plus quinacrine in vitro, and the drug combination improves survival of immunodeficient mice injected orthotopically with ATC cells as compared with mice administered either compound alone or doxorubicin. We also demonstrate that the combination of sorafenib and quinacrine is well tolerated in mice. At the molecular level, quinacrine and sorafenib inhibited expression of prosurvival MCL1, pSTAT3, and dampened NFκB signaling.
Conclusions: The combination of quinacrine and sorafenib targets emerging molecular hallmarks of ATC and shows promising results in clinically relevant models for the disease. Further testing of sorafenib plus quinacrine can be conducted in ATC patients. Clin Cancer Res; 22(24); 6192–203. ©2016 AACR.
PI3K Pathway Inhibition Achieves Potent Antitumor Activity in Melanoma Brain MetastasesIn VitroandIn Vivo
Authors: Niessner Heike , Schmitz Jennifer , Tabatabai Ghazaleh , Schmid Andreas M. , Calaminus Carsten , Sinnberg Tobias , Weide Benjamin , Eigentler Thomas K. , Garbe Claus , Schittek Birgit , Quintanilla-Fend Leticia , Bender Benjamin , Mai Marion , Praetorius Christian , Beissert Stefan , Schackert Gabriele , Muders Michael H. , Meinhardt Matthias , Baretton Gustavo B. , Dummer Reinhard , Flaherty Keith , Pichler Bernd J. , Kulms Dagmar , Westphal Dana , Meier Friedegund 
Published: June 2016

AbstractPurpose: Great advances have recently been made in treating patients with metastatic melanoma. However, existing therapies are less effective on cerebral than extracerebral metastases. This highlights the potential role of the brain environment on tumor progression and drug resistance and underlines the need for “brain-specific” therapies. We previously showed that the PI3K-AKT survival pathway is hyperactivated in brain but not extracerebral melanoma metastases and that astrocyte-conditioned medium activates AKT in melanoma cells in vitro. We therefore tested the PI3K inhibitor buparlisib as an antitumor agent for melanoma brain metastases.Experimental Design and Results: Buparlisib inhibited AKT activity, decreased proliferation, and induced apoptosis in metastatic melanoma cell lines and short-term brain melanoma cells, irrespective of their BRAF and NRAS mutation status. In addition, buparlisib inhibited hyperactivated AKT and induced apoptosis in melanoma cells that were stimulated with astrocyte-conditioned medium. The growth of tumors induced by injecting human BRAF- and NRAS-mutant metastatic melanoma cells into the brain of mice was significantly inhibited by buparlisib.Conclusions: These results emphasize the value of targeting the PI3K pathway as a strategy to develop drugs for melanoma brain metastases. Clin Cancer Res; 22(23); 5818–28. ©2016 AACR.
Delta One T Cells for Immunotherapy of Chronic Lymphocytic Leukemia: Clinical-Grade Expansion/Differentiation and Preclinical Proof of Concept
Authors: Almeida Afonso R. , Correia Daniel V. , Fernandes-Platzgummer Ana , da Silva Cláudia L. , da Silva Maria Gomes , Anjos Diogo Remechido , Silva-Santos Bruno 
Published: June 2016

Abstract
Purpose: The Vδ1+ subset of γδ T lymphocytes is a promising candidate for cancer immunotherapy, but the lack of suitable expansion/differentiation methods has precluded therapeutic application. We set out to develop and test (preclinically) a Vδ1+ T-cell–based protocol that is good manufacturing practice compatible and devoid of feeder cells for prompt clinical translation.
Experimental design: We tested multiple combinations of clinical-grade agonist antibodies and cytokines for their capacity to expand and differentiate (more than 2–3 weeks) Vδ1+ T cells from the peripheral blood of healthy donors and patients with chronic lymphocytic leukemia (CLL). We characterized the phenotype and functional potential of the final cellular product, termed Delta One T (DOT) cells, in vitro and in vivo (xenograft models of CLL).
Results: We describe a very robust two-step protocol for the selective expansion (up to 2,000-fold in large clinical-grade cell culture bags) and differentiation of cytotoxic Vδ1+ (DOT) cells. These expressed the natural cytotoxicity receptors, NKp30 and NKp44, which synergized with the T-cell receptor to mediate leukemia cell targeting in vitro. When transferred in vivo, DOT cells infiltrated tumors and peripheral organs, and persisted until the end of the analysis without showing signs of loss of function; indeed, DOT cells proliferated and produced abundant IFNγ and TNFα, but importantly no IL17, in vivo. Critically, DOT cells were capable of inhibiting tumor growth and preventing dissemination in xenograft models of CLL.
Conclusions: We provide a clinical-grade method and the preclinical proof of principle for application of a new cellular product, DOT cells, in adoptive immunotherapy of CLL. Clin Cancer Res; 22(23); 5795–804. ©2016 AACR.
External validation of the IMPROVE Bleeding Risk Assessment Model in medical patients
Authors: Rosenberg David J. , Press Anne , Fishbein Joanna , Lesser Martin , McCullagh Lauren , McGinn Thomas , Spyropoulos Alex C. 
Published: June 2016

SummaryThe IMPROVE Bleed Risk Assessment Model (RAM) remains the only bleed RAM in hospitalised medical patients using 11 clinical and laboratory factors. The aim of our study was to externally validate the IMPROVE Bleed RAM. A retrospective chart review was conducted between October 1, 2012 and July 31, 2014. We applied the point scoring system to compute risk scores for each patient in the validation sample. We then dichotomised the patients into those with a score <7 (low risk) vs ≥ 7 (high risk), as outlined in the original study, and compared the rates of any bleed, non-major bleed, and major bleed. Among the 12,082 subjects, there was an overall 2.6 % rate of any bleed within 14 days of admission. There was a 2.12 % rate of any bleed in those patients with a score of < 7 and a 4.68 % rate in those with a score ≥ 7 [Odds Ratio (OR) 2.3 (95 % CI=1.8–2.9), p<0.0001]. MB rates were 1.5 % in the patients with a score of < 7 and 3.2 % in the patients with a score of ≥ 7, [OR 2.2 (95 % CI=1.6–2.9), p<0.0001]. The ROC curve was 0.63 for the validation sample. This study represents the largest externally validated Bleed RAM in a hospitalised medically ill patient population. A cut-off point score of 7 or above was able to identify a high-risk patient group for MB and any bleed. The IMPROVE Bleed RAM has the potential to allow for more tailored approaches to thromboprophylaxis in medically ill hospitalised patients.Supplementary Material to this article is available online at www.thrombosis-online.com.
A Prospective Study of Ripple Mapping the Post-Infarct Ventricular Scar to Guide Substrate Ablation for Ventricular Tachycardia
Authors: Luther Vishal , Linton Nick W.F. , Jamil-Copley Shahnaz , Koa-Wing Michael , Lim Phang Boon , Qureshi Norman , Ng Fu Siong , Hayat Sajad , Whinnett Zachary , Davies D. Wyn , Peters Nicholas S. , Kanagaratnam Prapa 
Published: June 2016

Background—
Post-infarct ventricular tachycardia is associated with channels of surviving myocardium within scar characterized by fractionated and low-amplitude signals usually occurring late during sinus rhythm. Conventional automated algorithms for 3-dimensional electro-anatomic mapping cannot differentiate the delayed local signal of conduction within the scar from the initial far-field signal generated by surrounding healthy tissue. Ripple mapping displays every deflection of an electrogram, thereby providing fully informative activation sequences. We prospectively used CARTO-based ripple maps to identify conducting channels as a target for ablation.

Methods and Results—
High-density bipolar left ventricular endocardial electrograms were collected using CARTO3v4 in sinus rhythm or ventricular pacing and reviewed for ripple mapping conducting channel identification. Fifteen consecutive patients (median age 68 years, left ventricular ejection fraction 30%) were studied (6 month preprocedural implantable cardioverter defibrillator therapies: median 19 ATP events [Q1–Q3=4–93] and 1 shock [Q1–Q3=0–3]). Scar (<1.5 mV) occupied a median 29% of the total surface area (median 540 points collected within scar). A median of 2 ripple mapping conducting channels were seen within each scar (length 60 mm; initial component 0.44 mV; delayed component 0.20 mV; conduction 55 cm/s). Ablation was performed along all identified ripple mapping conducting channels (median 18 lesions) and any presumed interconnected late-activating sites (median 6 lesions; Q1–Q3=2–12). The diastolic isthmus in ventricular tachycardia was mapped in 3 patients and colocated within the ripple mapping conducting channels identified. Ventricular tachycardia was noninducible in 85% of patients post ablation, and 71% remain free of ventricular tachycardia recurrence at 6-month median follow-up.

Conclusions—
Ripple mapping can be used to identify conduction channels within scar to guide functional substrate ablation.
Assessment of Mitral Paravalvular Leakage After Mitral Valve Replacement Using Cardiac Computed Tomography
Authors: Suh Young Joo , Hong Geu-Ru , Han Kyunghwa , Im Dong Jin , Chang Suyon , Hong Yoo Jin , Lee Hye-Jeong , Hur Jin , Choi Byoung Wook , Chang Byung-Chul , Shim Chi Young , Kim Young Jin 
Published: June 2016

Background—
The diagnostic performance of cardiac computed tomography (CT) for detection of paravalvular leakage (PVL) after mitral valve replacement has not been investigated in a large population. We aimed to investigate the diagnostic accuracy of CT for diagnosis of mitral PVL using surgical findings as the standard reference and to compare the diagnostic performance of CT with those of transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE).

Methods and Results—
A total of 204 patients with previous mitral valve replacement who underwent cardiac CT were retrospectively included. The presence of mitral PVL was analyzed on CT, TTE, and TEE. In 78 patients who underwent redo-surgery, diagnostic performance for the detection of PVL for CT, TTE, and TEE were compared with surgical findings as the standard reference. The location of mitral PVL on CT and TEE was compared with surgical findings. Mitral PVL was present in 18.1% (37/204) on CT, in 16.2% (32/198) on TTE, and in 42.6% (29/68) on TEE. On the surgical field, PVL was identified in 41.0% (32/78). The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy for detection of PVL were 96.9%, 97.8%, 96.9%, 97.8%, and 97.4% for CT; 81.3%, 95.6%, 92.9%, 87.8%, and 89.6% for TTE; and 96.2%, 95.8%, 96.2%, 95.8%, and 96.0% for TEE. CT and TEE identified the correct location of PVL in 75.9% (22/29) and 85.6% (19/23).

Conclusions—
Cardiac CT may have better diagnostic accuracy compared with TTE for the detection of mitral PVL and may be comparable to TEE for the detection and localization of PVL.
Outcomes With the Use of the Retrograde Approach for Coronary Chronic Total Occlusion Interventions in a Contemporary Multicenter US Registry
Authors: Karmpaliotis Dimitri , Karatasakis Aris , Alaswad Khaldoon , Jaffer Farouc A. , Yeh Robert W. , Wyman R. Michael , Lombardi William L. , Grantham J. Aaron , Kandzari David E. , Lembo Nicholas J. , Doing Anthony , Patel Mitul , Bahadorani John N. , Moses Jeffrey W. , Kirtane Ajay J. , Parikh Manish , Ali Ziad A. , Kalra Sanjog , Nguyen-Trong Phuong-Khanh J. , Danek Barbara A. , Karacsonyi Judit , Rangan Bavana V. , Roesle Michele K. , Thompson Craig A. , Banerjee Subhash , Brilakis Emmanouil S. 
Published: June 2016

Background—
We sought to examine the efficacy and safety of chronic total occlusion percutaneous coronary intervention using the retrograde approach.

Methods and Results—

We compared the outcomes of the retrograde versus antegrade-only approach to chronic total occlusion percutaneous coronary intervention among 1301 procedures performed at 11 experienced US centers between 2012 and 2015. The mean age was 65.5±10 years, and 84% of the patients were men with a high prevalence of diabetes mellitus (45%) and previous coronary artery bypass graft surgery (34%). Overall technical and procedural success rates were 90% and 89%, respectively, and in-hospital major adverse cardiovascular events occurred in 31 patients (2.4%). The retrograde approach was used in 539 cases (41%), either as the initial strategy (46%) or after a failed antegrade attempt (54%). When compared with antegrade-only cases, retrograde cases were significantly more complex, both clinically (previous coronary artery bypass graft surgery prevalence, 48% versus 24%;
P
<0.001) and angiographically (mean Japan-chronic total occlusion score, 3.1±1.0 versus 2.1±1.2;
P
<0.001) and had lower technical success (85% versus 94%;
P
<0.001) and higher major adverse cardiovascular events (4.3% versus 1.1%;
P
<0.001) rates. On multivariable analysis, the presence of suitable collaterals, no smoking, no previous coronary artery bypass graft surgery, and left anterior descending artery target vessel were independently associated with technical success using the retrograde approach.

Conclusions—
The retrograde approach is commonly used in contemporary chronic total occlusion percutaneous coronary intervention, especially among more challenging lesions and patients. Although associated with lower success and higher major adverse cardiovascular event rates in comparison to antegrade-only crossing, retrograde percutaneous coronary intervention remains critical for achieving overall high success rates.
Impact of Sleep‐Disordered Breathing on Long‐Term Outcomes in Patients With Acute Coronary Syndrome Who Have Undergone Primary Percutaneous Coronary Intervention
Authors: Mazaki Toru , Kasai Takatoshi , Yokoi Hiroyoshi , Kuramitsu Shoichi , Yamaji Kyohei , Morinaga Takashi , Masuda Hisaki , Shirai Shinichi , Ando Kenji 
Published: June 2016

Background

Sleep‐disordered breathing (
SDB
) has been recognized as an important risk factor for cardiovascular diseases; however, the impact of
SDB
on long‐term outcomes in patients with acute coronary syndrome has not been fully evaluated.

Methods and Results

We performed overnight cardiorespiratory monitoring of 241 patients with acute coronary syndrome who were successfully treated with primary percutaneous coronary intervention between January 2005 and December 2008. The presence of
SDB
was defined as apnea–hypopnea index ≥5 events per hour. The end point was incidence of major adverse cardiocerebrovascular events, defined as a composite of all‐cause death, recurrence of acute coronary syndrome, nonfatal stroke, and hospital admission for congestive heart failure. Patients were followed for a median period of 5.6 years. Among the 241 patients who were finally enrolled, comorbidity of
SDB
with acute coronary syndrome was found in 126 patients (52.3%). The cumulative incidence of major adverse cardiocerebrovascular events was significantly higher in patients with
SDB
than in those without
SDB
(21.4% versus 7.8%,
P
=0.006). Multivariable analysis revealed that the presence of
SDB
was a significant predictor of major adverse cardiocerebrovascular events (hazard ratio 2.28, 95%
CI
1.06–4.92;
P
=0.035).

Conclusions

The study's results showed that the presence of
SDB
among patients with acute coronary syndrome following primary percutaneous coronary intervention is associated with a higher incidence of major adverse cardiocerebrovascular events during long‐term follow‐up.
Gastrodia cajanoae (Orchidaceae: Epidendroideae: Gastrodieae), a new species from the Philippines
Authors: PELSER PIETER B. , DOBLE KIM JOHN S. , O’BYRNE PETER , ORMEROD PAUL , BARCELONA JULIE F. 
Published: June 2016

Gastrodia Brown (1810: 330) is a holomycotrophic terrestrial orchid genus of c. 65 species with an Old World distribution and centre of diversity in Southeast Asia (Cribb et al. 2010, Huang et al. 2015, Ong 2015). In the Philippines, two species are thus far known: G. javanica (Blume, 1825: 421) Lindley (1840: 384) and G. verrucosa Blume (1856: 175). Both have a widespread distribution in northern Malesia and southern East Asia. During fieldwork for the Co’s Digital Flora of the Philippine project (Pelser et al. 2011 onwards) in early December 2012, Gastrodia plants were photographed that belong to a third Philippine species. These plants were observed in three areas on the island of Mindanao: Mt. Apo Natural Park (North Cotabato Prov.) and two sites in Mt. Kitanglad Range Natural Park (Lantapan and Baungon municipalities; Bukidnon Prov.). In December 2015, plants belonging to the same species were collected in Northern Negros Natural Park (Victorias City, Negros Occidental Prov., Negros) and in March 2016 plants were photographed in Barlig (Mountain Prov., Luzon). Morphological studies showed that this species is distinct from all Gastrodia species except G. spathulata (Carr, 1935: 180) Wood (in Wood et al. 2011: 355) in having petals that are considerably shorter than the calyx tube and separate from it about half way along the inner surface of the tube. It differs from G. spathulata in the longer adnation of the petals to the calyx tube, the shape of the petals and their lack of indumentum, and characters of the lip ridges. Assuming that these morphological differences are an indication of reproductive isolation, we name and describe these plants here as a new species under a biological species concept (Mayr 2000). This new addition brings the total number of Philippine Gastrodia species to three.